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Patent 2459219 Summary

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(12) Patent Application: (11) CA 2459219
(54) English Title: METHODS OF DIAGNOSIS OF CANCER COMPOSITIONS AND METHODS OF SCREENING FOR MODULATORS OF CANCER
(54) French Title: PROCEDES DE DIAGNOSTIC DU CANCER, COMPOSITIONS ET PROCEDES DE CRIBLAGE DE MODULATEURS DU CANCER
Status: Dead
Bibliographic Data
(51) International Patent Classification (IPC):
  • C07K 14/47 (2006.01)
  • G01N 33/574 (2006.01)
  • C12Q 1/68 (2006.01)
(72) Inventors :
  • AFAR, DANIEL (United States of America)
  • AZIZ, NATASHA (United States of America)
  • GISH, KURT C. (United States of America)
  • HEVEZI, PETER A. (United States of America)
  • MACK, DAVID H. (United States of America)
  • WILSON, KEITH E. (United States of America)
  • ZLOTNIK, ALBERT (United States of America)
(73) Owners :
  • PDL BIOPHARMA, INC. (United States of America)
(71) Applicants :
  • PROTEIN DESIGN LABS, INC. (United States of America)
(74) Agent: NORTON ROSE FULBRIGHT CANADA LLP/S.E.N.C.R.L., S.R.L.
(74) Associate agent:
(45) Issued:
(86) PCT Filing Date: 2002-09-17
(87) Open to Public Inspection: 2003-03-27
Examination requested: 2007-09-14
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): Yes
(86) PCT Filing Number: PCT/US2002/029560
(87) International Publication Number: WO2003/025138
(85) National Entry: 2004-03-17

(30) Application Priority Data:
Application No. Country/Territory Date
60/323,469 United States of America 2001-09-17
60/323,887 United States of America 2001-09-20
60/350,666 United States of America 2001-11-13
60/355,145 United States of America 2002-02-08
60/355,257 United States of America 2002-02-08
60/372,246 United States of America 2002-04-12

Abstracts

English Abstract




Described herein are genes whose expression are up-regulated or down-regulated
in specific cancers. Related methods and compositions that can be used for
diagnosis and treatment of those cancers are disclosed. Also described herein
are methods that can be used to identify modulators of selected cancers.


French Abstract

L'invention concerne des gènes dont l'expression est régulée positivement ou négativement dans des cancers spécifiques ; des procédés et des compositions associées pouvant servir à diagnostiquer et à traiter ces cancers ; et des procédés pouvant servir à identifier des modulateurs de cancers sélectionnés.

Claims

Note: Claims are shown in the official language in which they were submitted.




WHAT IS CLAIMED IS:

1. A method for determining the presence or absence of a pathological
cell in a patient, said method comprising detecting a nucleic acid comprising
a
sequence at least 80% identical to a sequence as described in Tables 2A-68 in
a
biological sample from said patient, thereby determining the presence or
absence of
said pathological cell.

2. The method of Claim 1 wherein:
a) said pathology is described in Table 1, including a cancer; and/or
b) said biological sample comprises isolated nucleic acids.

3. The method of Claim 1, wherein said biological sample is tissue from
an organ which is affected by said pathology of Table 1, including a cancer.

4. The method of Claim 2, wherein said nucleic acids are mRNA.

5. The method of Claim 2:
further comprising a step of amplifying nucleic acids before said step of
detecting said nucleic acid; or
where said detecting is of a protein encoded by said nucleic acid.

6. The method of Claim 1, wherein said nucleic acid comprises a
sequence as described in Tables 2A-68.

7. The method of Claim 2, wherein:
said detecting step is carried out by:
i) using a labeled nucleic acid probe;
ii) utilizing a biochip comprising a sequence at least 80% identical to a
sequence as described in Tables 2A-68; or
iii) detecting a polypeptide encoded by said nucleic acid; or
said patient is:
i) undergoing a therapeutic regimen to treat said pathology of Table 1; or
ii) is suspected of having said pathology or cancer.

8. As isolated nucleic acid molecule comprising a sequence as described
in Tables 2A-68.

764



9. The nucleic acid molecule of Claim 8, which is labeled.

10. An expression vector comprising the nucleic acid of Claim 8.

11. A host cell comprising the expression vector of Claim 10.

12. An isolated polypeptide which is encoded by a nucleic acid molecule
comprising a sequence as described in Tables 2A-68.

13. An antibody that specifically binds a polypeptide of Claim 12.

14. The antibody of Claim 13:
a) conjugated to an effector component;
b) conjugated to a detectable label, including a fluorescent label, a
radioisotope, or a
cytotoxic chemical;
c) which is an antibody fragment; or
d) which is a humanized antibody.

15. A method for specifically targeting a compound to a pathological cell in a
patient, said method comprising administering to said patient an antibody of
Claim 13,
thereby providing said targetting.

16. A method for determining the presence or absence of a pathological cell in
a
patient, said method comprising contacting a biological sample with an
antibody of Claim 13.

17. The method of Claim 16, wherein:
a) said antibody is conjugated to:
i) an effector component; or
ii) a fluorescent label; or
b) said biological sample is a blood, serum, urine, or stool sample.

18. A method for identifying a compound that modulates a pathology-associated
polypeptide, said method comprising the steps of:

765



a) contacting said compound with a pathology-associated polypeptide, said
polypeptide encoded by a polynucleotide that selectively hybridizes to a
sequence
at least 80% identical to a sequence as described in Tables 2A-68; and
b) determining the functional effect of said compound upon said polypeptide.

19. A drug screening assay comprising the steps of:
a) administering a test compound to a mammal having a pathology of Table 1 or
a
cell isolated therefrom; and
b) comparing the level of gene expression of a polynucleotide that selectively
hybridizes to a sequence at least 80% identical to a sequence as described in
Tables 2A-68 in a treated cell or mammal with the level of gene expression of
said
polynucleotide in a control cell or mammal, wherein a test compound that
modulates said level of expression of the polynucleotide is a candidate for
the
treatment of said pathology.

766


Description

Note: Descriptions are shown in the official language in which they were submitted.





DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.
CECI EST LE TOME 1 DE 4
CONTENANT LES PAGES 1 A 211
NOTE : Pour les tomes additionels, veuillez contacter 1e Bureau canadien des
brevets
JUMBO APPLICATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME
THIS IS VOLUME 1 OF 4
CONTAINING PAGES 1 TO 211
NOTE: For additional volumes, please contact the Canadian Patent Office
NOM DU FICHIER / FILE NAME
NOTE POUR LE TOME / VOLUME NOTE:


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
METHODS OF DIAGNOSIS OF CANCER, COMPOSITIONS AND METHODS OF
SCREENING FOR MODULATORS OF CANCER
CROSS-REFERENCES TO RELATED APPLICATIONS
This application claims priority to USSN 60/323,469, filed Setember 17, 2001;
USSN
60/355,145, filed February 8, 2002; USSN 60/369,899, filed April 4, 2002; USSN
60/323,887,
filed September 20, 2001; USSN 60/355,257, filed February 8, 2002; USSN
60/325,114, filed
September 25, 2001; USSN 60/340,944, filed October 29, 2001; USSN 60/350,666,
filed
LO November 13, 2001; and USSN 60/372,246, filed April 12, 2002; each of which
is incorporated
herein by reference for all purposes.
FIELD OF THE 1NVENTION
The invention relates to the identification of nucleic acid and protein
expression profiles
and nucleic acids, products, and antibodies thereto that are involved in
cancer; and to the use of
15 such expression profiles and compositions in the diagnosis, prognosis, and
therapy of cancer.
The invention further relates to methods for identifying and using agents
and/or targets that
modulate cancer.
BACKGROUND OF THE INVENTION
Cancer is a major cause of morbidity in the United States. For example, in
1996, the
20 American Cancer Society estimated that 1,359,150 people were diagnosed with
a malignant
neoplasm and 554,740 died from one of these diseases. Cancer is responsible
for 23.9 percent
of all American deaths and is exceeded only by heart disease as a cause of
mortality (33
percent). Unfortunately, cancer mortality is increasing and sometime early in
this century,
cancer is expected to become the leading cause of mortality in the United
States as it already is
25 in Japan.
Cancers share the charactaristic of disordered control over normal cell
division, growth,
and differentiation. Their initial clinical manifestations are extremely
heterogeneous, with over
70 types of cancer arising in virtually every organ and tissue of the body.
Moreover, some of
those similarly classified cancer types may represent multiple different
molecular diseases.
30 Unfortunately, some cancers may be virtually asymptomatic until late in the
disease course,
when treatment is more difficult, and prognosis grim.


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
Treatment for cancer typically includes surgery, chemotherapy, and/or
radiation therapy.
Although nearly 50 percent of cancer patients can be effectively treated using
these methods,
the current therapies all induce serious side effects which diminish quality
of life. The
identification of novel therapeutic targets and diagnostic markers will be
important for
improving the diagnosis and treatment of cancer patients.
Recent advances in molecular medicine have increased the interest in tumor-
specific
antigens that could serve as targets for various immunotherapeutic or small
molecule strategies.
Antigens suitable for immunotherapeutic strategies should be highly expressed
in cancer tissues,
preferably accessible from the vasculature and at the cell surface, and
ideally not expressed in
normal adult tissues. Expression in tissues that are dispensable for life,
however, may be
tolerated, e.g., reproductive organs. Examples of antigens that are currently
available for the
detection and treatment of certain cancers include Her2/neu and the B-cell
antigen CD20.
Humanized monclonal antibodies directed to Her2/neu (Herceptin~/trastuzumab)
are currently
in use for the treatment of metastatic breast cancer. See Ross and Fletcher
(1998) Stem Cells
16:413-428. Similarly, anti-CD20 monoclonal antibodies (Rituxin~/rituximab)
are used to
effectively treat non-Hodgkin's lymphoma. See Maloney, et al. (1997) Blood
90:2188-2195;
Leget and Czuczman (1998) Curr. Opin. Oncol. 10:548-551.
The elucidation of a role for novel proteins and compounds in disease states
for
identification of therapeutic targets and diagnostic markers is valuable for
improving the current
treatment of cancer patients. Accordingly, provided herein are molecular
targets for therapeutic
intervention in various defined cancers. Additionally, provided herein are
methods that can be
used in diagnosis and prognosis of cancer. Further provided are methods that
can be used to
screen candidate bioactive agents for the ability to modulate cancer.
SUMMARY OF THE INVENTION
The present invention provides methods for determining the presence or absence
of a pathological cell in a patient, the method comprising detecting a nucleic
acid comprising a
sequence at least 80% identical to a sequence as described in Tables 2A-68 in
a biological
sample from the patient, thereby determining the presence or absence of the
pathological cell.
In certain embodiments of the method, the pathology is described in Table 1,
including a
cancer; the biological sample comprises isolated nucleic acids; the nucleic
acids are mRNA; the
biological sample is tissue from an organ which is affected by the pathology
of Table 1,
including a cancer; a further step is used of amplifying nucleic acids before
the step of detecting
2


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
the nucleic acid; the detecting is of a protein encoded by the nucleic acid;
the nucleic acid
comprises a sequence as described in Tables 2A-68; the detecting step is
carned out by using a
labeled nucleic acid probe, utilizing a biochip comprising at sequence at
least 80% identical to a
sequence as described in Tables 2A-68, or detecting a polypeptide encoded by
the nucleic acid;
or the patient is undergoing a therapeutic regimen to treat the pathology of
Table 1, or is
suspected of having the pathology or cancer.
Compostions are also provided, e.g., an isolated nucleic acid molecule
comprising a
sequence as described in Tables 2A-68, including, e.g., those which are
labeled; an expression
vector comprising such nucleic acid; a host cell comprising such expression
vector; an isolated
polypeptide which is encoded by such a nucleic acid molecule comprising a
sequence as
described in Tables 2A-68; or an antibody that specifically binds the
polypeptide. In particular
embodiments, the antibody is: conjugated to an effector component, is
conjugated to a
detectable label (including, e.g., a fluorescent label, a radioisotope, or a
cytotoxic chemical), an
antibody fragment, or is a humanized antibody.
Additional methods are provided, including methods for specifically targeting
a
compound to a pathological cell in a patient, the method comprising
administering to the patient
an antibody, as described, thereby providing the targetting. Others include,
e.g., methods for
determining the presence or absence of a pathological cell in a patient, the
methods comprising
contacting a biological sample with an antibody, as described. In more
particular methods, the
antibody is: conjugated to an effector component, or to a fluorescent label;
or the biological
sample is a blood, serum, urine, or stool sample.
Further methods include those for identifying a compound that modulates a
pathology-
associated polypeptide, the method comprising steps of: contacting the
compound with a
pathology-associated polypeptide, the polypeptide encoded by a polynucleotide
that selectively
hybridizes to a sequence at least 80% identical to a sequence as described in
Tables 2A-68; and
determining the functional effect of the compound upon the polypeptide.
Another drug
screening assay method comprises steps of administering a test compound to a
mammal having
a pathology of Table 1 or a cell isolated therefrom; and comparing the level
of gene expression
of a polynucleotide that selectively hybridizes to a sequence at least 80%
identical to a sequence
as described in Tables 2A-68 in a treated cell or mammal with the level of
gene expression of
the polynucleotide in a control cell or mammal, wherein a test compound that
modulates the
level of expression of the polynucleotide is a candidate for the treatment of
the pathology.
3


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the objects outlined above, the present invention provides
novel
methods for diagnosis and prognosis evaluation for various disorders, e.g.,
angiogenesis,
fibrosis, and various defined forms of cancer, including metastatic cancer, as
well as methods
S for screening for compositions which modulate such conditions. Also provided
are methods for
treating such disorders or cancers. See, e.g., American Society of Clinical
Oncology (ed. 2001)
ASCO Curnculum: Symptom Management Kendall/Hunt, ISBN: 0787277851; Bonadonna,
et
al. (2001) Textbook of Breast Cancer (2d ed.) Dunitz Martin, ISBN: 1853178241;
Devita and
Hellman (eds. 2001) Cancer Principles and Practice of Oncology (2 vols.),
Lippincott Williams,
ISBN: 0781723876; Howell, et al. (2001) Breast Cancer Isis Medical Media,
ISBN:
1901865584; Kaye and Laws (2001) Brain Tumours: An Encyclopedic Approach (2d
ed.)
Churchill Livingstone, ISBN: 0443064261; Mihm, et al. (2001) The Melanocytic
Proliferation:
A Comprehensive Textbook of Pigmented Lesions Wiley-Liss, ISBN: 0471252719;
Montgomery and Aaron (2001) Clinical Pathology of Soft-Tissue Tumors Marcel
Dekker,
ISBN: 0824702905; Petrovich, et al. (eds. 2001) Combined Modalit,~r of Central
Nervous
System Tumors (Medical Radiology) Springer Verlag, ISBN: 3540660534; Rosen
(2001)
Rosen's Breast Patholo~y Lippincott Williams and Wilkins, ISBN: 0781723795;
Shah, et al.
(2001) Oral Cancer Isis Medical Media, ISBN: 189906687X; Weiss and Goldblum
(2001)
Enzin er and Weiss's Soft Tissue Tumors (4th ed.) Mosby, ISBN: 0323012000;
Abeloff, et al.
(eds. 2000) Clinical Oncology (2d ed.) Churchill Livingstone, ISBN:
044307545X; American
Society of Clinical Oncology (ed. 2000) Cancer Genetics and Cancer
Predisposition Testing
Kendall/Hunt, ISBN: 0787276154; Fletcher (2000) Diagnostic Histopathology of
Tumors (2
vols. 2d ed.) Churchill Livingstone, ISBN: 0443079927; Vogelzang (ed. 2000)
Comprehensive
Textbook of GenitourinarYOncolo~y (2d ed.) Lippincott Williams and Wilkins,
ISBN:
0683306456; Holland, et al. (eds. 2000) Holland-Frei Cancer Medicine (Book
with CD-ROM
5th ed.) Decker, ISBN: 1550091131; Turnsi, et al. (2000) Lung Cancer Isis
Medical Media,
ISBN: 1901865428; Bartolozzi and Lencioni (eds. 1999) Liver Mali~ancies:
Diagnostic and
Interventional Radiolo~y (Medical Radiology) Springer Verlag, ISBN:
3540647562; Gasparini
(ed. 1999) Pro ostic Variables in Node-Negative and Node-Positive Breast
Cancer Kluwer,
ISBN: 0792384474; Hansen (ed. 1999) The LASLC Textbook of Lung Cancer:
International
Association for the Study of Lung Cancer Dunitz Martin, ISBN: 1853177083;
Raghavan, et al.
(eds. 1999) Textbook of Uncommon Cancer (2nd ed.) Wiley, ISBN: 0471929212;
Thawley, et
4


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
al. (eds. 1999) Comprehensive Management of Head and Neck Tumors (2 vols.)
Saunders,
ISBN: 0721655823; Whittaker and Holmes (eds. 1999) Leukemia and Related
Disorders (3d
ed.) Blackwell Science, ISBN: 0865426074; Aapro (ed. 1998) OncoMedia: Medical
Oncolo~y
(CD-ROM) Elsevier Science, ISBN: 0080427480; Abeloff (1998) Clinical Oncolo~y
(Library
Version 2 CD-ROM Individual Version 2.0 Windows and Macintosh) Harcourt Brace,
ISBN:
0443075557; Benson (ed. 1998) Gastrointestinal Oncolo~y (Cancer Treatment and
Research,
CTAR 98) Kluwer, ISBN: 0792382056; Brambilla and Brambilla (eds. 1998)
Lun~LTumors:
Fundamental Biology and Clinical Management (Vol 124) Marcel Dekker, ISBN:
0824701607;
Canellos, et al. (eds. 1998) The Lym~homas Saunders, ISBN: 0721650309;
Greenspan and
Remagen (1998) Differential Diagnosis of Tumors and Tumor-Like Lesions of
Bones and Joints
Lippincott Williams and Wilkins Publishers, ISBN: 0397517106; Hiddemann (ed.
1998) Acute
Leukemias VII- Experimental Approaches and Novel Therapies (Haematologie Und
Bluttransfusion, Vol 39), Springer Verlag, ISBN: 3540635041; Husband and
Reznek (1998)
Imaging in Oncolo~y (2 vols.) Mosby, ISBN: 1899066489; Leibel and Phillips
(eds. 1998)
Textbook of Radiation Oncolo~y Saunders, ISBN: 0721653367; Maloney and Miller
(eds.
1998) Cutaneous Oncology' Patho_physiology Diagnosis and Management Blackwell
Science,
ISBN: 0865425175; Mittal, et al. (eds. 1998) Advances in Radiation Therapy
Kluwe, ISBN:
0792399811; Oldham (ed. 1998) Principles of Cancer Biotherapy (3d ed.) Kluwer,
ISBN:
0792335074; Ozols (ed. 1998) Gynecolo~ic Oncolo~y Kluwer, ISBN: 0792380703;
Parkin, et
al. (eds. 1998) Cancer Incidence in Five Continents (Iarc Scientific
Publications, No 143)
Oxford University Press, ISBN: 9283221435; Perez and Brady (eds. 1998)
Principles and
Practice of Radiation Oncolo~y Lippincott Williams and Wilkins, ISBN:
0397584164; Black, et
al. (eds. 1997) Cancer of the Nervous System Blackwell Science, ISBN:
0865423849;
Bonadonna, et al. (1997) Textbook of Breast Cancer: A Clinical Guide to
Therapy Blackwell
Science, ISBN: 1853173487; Pollock (ed. 1997) Sur ical Oncolo~y Kluwer, ISBN:
0792399005; Sheaves, et al. (eds. 1997) Clinical Endocrine Oncolo~y Blackwell
Science,
ISBN: 086542862X; Vahrson (1997) Radiation Oncolo_gu of Gynecological Cancers
Springer
Verlag, ISBN: 0387567682; Walterhouse and Cohn (eds. 1997) Diagnostic and
Therapeutic
Advances in Pediatric Oncolo~y Kluwer, ISBN: 0792399781; Aisner (ed. 1996)
Comprehensive
Textbook of Thoracic Oncolo~y Lippincott, Williams and Wilkins, ISBN:
0683000624;
Bertino, et al. (eds. 1996) Encyclopedia of Cancer (3 vols.) Academic, ISBN:
012093230X;
Cavalli, et al. (1996) Textbook of Medical Oncolo~y Dunitz Martin, ISBN:
1853172901;
5


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
Peckham, et al. (eds. 1995) Oxford Textbook of Oncolo~y (2-Vols.) Oxford
University Press,
ISBN: 0192616854; and Freireich and I~antarjian (eds. 1996) Molecular Genetics
and Therapy
of Leukemia (Cancer Treatment and Research, V. 84) Kluwer, ISBN: 0792339126.
In particular, identification of markers selectively expressed on defined
cancers allows
for use of that expression in diagnostic, prognostic, or therapeutic methods.
As such, the
invention defines various .compositions, e.g., nucleic acids, polypeptides,
antibodies, and small
molecule agonists/antagonists, which will be useful to selectively identify
those markers. For
example, therapeutic methods may take the form of protein therapeutics which
use the marker
expression for selective localization or modulation of function (for those
markers which have a
causative disease effect), for vaccines, identification of binding partners,
or antagonism, e.g.,
using antisense or RNAi. The markers may be useful for molecular
characterization of subsets
of the diseases, e.g., as provided in Table 1, which subsets may actually
require very different
treatments. Moreover, the markers may also be important in related diseases to
the specific
disorders and cancers, e.g., which affect similar tissues in non-malignant
diseases, or have
similar mechanisms of induction/maintenance. Metastatic processes or
characteristics may also
be targeted. Diagnostic and prognostic uses are made available, e.g., to
subset related but
distinct diseases, or to determine treatment strategy. The detection methods
may be based upon
nucleic acid, e.g., PCR or hybridization techniques, or protein, e.g., ELISA,
imaging, IHC, etc.
The diagnosis may be qualitative or quantitative, and may detect increases or
decreases in
expression levels.
Tables 2B-66C provide unigene cluster identification numbers for the
nucleotide
sequence of genes that exhibit increased or decreased expression in cancer
samples, particularly
sequences involved in angiogenisis, prostate cancer (including androgen
independent and taxol
resistant prostate cancer), breast cancer, colorectal cancer, cervical cancer,
bladder cancer, lung
cancer, ovarian cancer, uterine cancer, glioblastoma, Ewing saxeoma, and lung
fibrosis. Tables
2A-67 also provide an exemplar accession number that provides a nucleotide
sequence that is
part of the unigene cluster.
Definitions
The term "cancer protein" or "cancer polynucleotide" or "cancer-associated
transcript"
refers to nucleic acid and polypeptide polymorphic variants, alleles, mutants,
and interspecies
homologues that: (1) have a nucleotide sequence that has greater than about
60% nucleotide
sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably about 92%, 94%,
96%, 97%,
6


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
98%, or 99% or greater nucleotide sequence identity, preferably over a region
of over a region
of at least about 25, 50, 100, 200, 500, 1000, or more nucleotides, to a
nucleotide sequence of or
associated with a gene of Tables 1-68; (2) bind to antibodies, e.g.,
polyclonal antibodies, raised
against an immunogen comprising an amino acid sequence encoded by a nucleotide
sequence of
or associated with a gene of Tables 1-68, and conservatively modified variants
thereof; (3)
specifically hybridize under stringent hybridization conditions to a nucleic
acid sequence, or the
complement thereof of Tables 1-68 and conservatively modified variants
thereof; or (4) have an
amino acid sequence that has greater than about 60% amino acid sequence
identity, 65%, 70%,
75%, 80%, 85%, preferably 90%, 91%, 93%, 95%, 97%, 98%, or 99% or greater
amino
sequence identity, preferably over a region of over a region of at least about
25, S0, 100, 200,
500, 1000, or more amino acids, to an amino acid sequence encoded by a
nucleotide sequence
of or associated with a gene of Tables 1-68. A polynucleotide or polypeptide
sequence is
typically from a mammal including, but not limited to, primate, e.g., human;
rodent, e.g., rat,
mouse, hamster; cow, pig, horse, sheep, or other mammal. A "cancer
polypeptide" and a
"cancer polynucleotide," include both naturally occurring or recombinant
forms.
A "full length" cancer protein or nucleic acid refers to a cancer polypeptide
or
polynucleotide sequence, or a variant thereof, that contains elements normally
contained in one
or more naturally occurring, wild type cancer polynucleotide or polypeptide
sequences. The
"full length" may be prior to, or after, various stages of post-translational
processing or splicing,
including alternative splicing.
"Biological sample" as used herein is a sample of biological tissue or fluid
that contains
nucleic acids or polypeptides, e.g., of a cancer protein, polynucleotide, or
transcript. Such
samples include, but are not limited to, tissue isolated from primates, e.g.,
humans, or rodents,
e.g., mice, and rats. Biological samples may also include sections of tissues
such as biopsy and
autopsy samples, frozen sections taken for histologic purposes, archival
samples, blood, plasma,
serum, sputum, stool, tears, mucus, hair, skin, etc. Biological samples also
include explants and
primary and/or transformed cell cultures derived from patient tissues. A
biological sample is
typically obtained from a eukaryotic organism, most preferably a mammal such
as a primate
e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat,
mouse; rabbit; or a
bird; reptile; or fish. Livestock and domestic animals are of interest.
"Providing a biological sample" means to obtain a biological sample for use in
methods
described in this invention. Most often, this will be done by removing a
sample of cells from an
7


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
animal, but can also be accomplished by using previously isolated cells (e.g.,
isolated by
another person, at another time, and/or for another purpose), or by performing
the methods of
the invention in vivo. Archival tissues or materials, having treatment or
outcome history, will
be particularly useful.
The terms "identical" or percent "identity," in the context of two or more
nucleic acids or
polypeptide sequences, refer to two or more sequences or subsequences that are
the same or
have a specified percentage of amino acid residues or nucleotides that are the
same (e.g., about
70% identity, preferably 75%, 80%, 85%, 90%, 91%, 93%, 95%, 97%, 98%, 99%, or
higher
identity over a specified region, when compared and aligned for maximum
correspondence over
a comparison window or designated region) as measured using, e.g., a BLAST or
BLAST 2.0
sequence comparison algorithms with default parameters described below, or by
manual
alignment and visual inspection (see, e.g., NCBI web site
http://www.ucbi.nlm.nih.gov/BLAST/
or the like). Such sequences are then said to be "substantially identical."
This definition also
refers to, or may be applied to, the complement of a test sequence. The
definition also includes
sequences that have deletions and/or insertions, substitutions, and naturally
occurring, e.g.,
polymorphic or allelic variants, and man-made variants. As described below,
the preferred
algorithms can account for gaps and the like. Preferably, identity exists over
a region that is at
least about 25 amino acids or nucleotides in length, or more preferably over a
region that is 50=
100 amino acids or nucleotides in length.
For sequence comparison, typically one sequence acts as a reference sequence,
to which
test sequences are compared. When using a sequence comparison algorithm, test
and reference
sequences are entered into a computer, subsequence coordinates are designated,
if necessary,
and sequence algorithm program parameters are designated. Preferably, default
program
parameters can be used, or alternative parameters can be designated. The
sequence comparison
algorithm then calculates the percent sequence identities for the test
sequences relative to the
reference sequence, based on the program parameters.
A "comparison window", as used herein, includes reference to a segment of
contiguous
positions selected from the group consisting typically of from 20 to 600,
usually about 50 to
about 200, more usually about 100 to about 150, in which a sequence may be
compared to a
reference sequence of the same number of contiguous positions after the two
sequences are
optimally aligned. Methods of alignment of sequences for comparison are well-
known.
Optimal alignment of sequences for comparison can be conducted, e.g., by the
local homology
8


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
algorithm of Smith and Waterman (1981) Adv. Appl. Math. 2:482-489, by the
homology
alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol. 48:443-453,
by the search
for similarity method of Pearson and Lipman (1988) Proc. Nat'1. Acad. Sci. USA
85:2444-2448,
by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and
TFASTA
in the Wisconsin Genetics Software Package, Genetics Computer Group, 575
Science Dr.,
Madison, WI), or by manual alignment and visual inspection (see, e.g.,
Ausubel, et al. (eds.
1995 and supplements) Current Protocols in Molecular Biolo~y Wiley).
Preferred examples of algorithms that are suitable for determining percent
sequence
identity and sequence similarity include the BLAST and BLAST 2.0 algorithms,
which are
described in Altschul, _et al. (1977) Nuc. Acids Res. 25:3389-3402 and
Altschul, et al. (1990) J.
Mol. Biol. 215:403-410. BLAST and BLAST 2.0 are used, with the parameters
described
herein, to determine percent sequence identity for the nucleic acids and
proteins of the
invention. Software for performing BLAST analyses is publicly available
through the National
Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov~. This
algorithm involves
first identifying high scoring sequence pairs (HSPs) by identifying short
words of length W in
the query sequence, which either match or satisfy some positive-valued
threshold score T when
aligned with a word of the same length in a database sequence. T is referred
to as the
neighborhood word score threshold (Altschul, et al., supra). These initial
neighborhood word
hits act as seeds for initiating searches to fmd longer HSPs containing them.
The word hits are
extended in both directions along each sequence for as far as the cumulative
alignment score
can be increased.-Cumulative scores are calculated using, e.g., for nucleotide
sequences, the
parameters M (reward score for a pair of matching residues; always > 0) and N
(penalty score
for mismatching residues; always < 0). For amino acid sequences, a scoring
matrix is used to
calculate the cumulative score. Extension of the word hits in each direction
are halted when: the
cumulative alignment score falls off by the quantity X from its maximum
achieved value; the
cumulative score goes to zero or below, due to the accumulation of one or more
negative-
scoring residue alignments; or the end of either sequence is reached. The
BLAST algorithm
parameters W, T, and X determine the sensitivity and speed of the alignment.
The BLASTN
program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an
expectation (E)
o~f 10, M=5, N=-4 and a comparison of both strands. For amino acid sequences,
the BLASTP
program uses as defaults a wordlength of 3, and expectation (E) of 10, and the
BLOSUM62
9


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scoring matrix (see Henikoff and Henikoff (1992) Proc. Natl. Acad. Sci. USA
89:10915-919)
alignments (B) of 50, expectation (E) of 10, M=S, N=-4, and a comparison of
both strands.
The BLAST algorithm also performs a statistical analysis of the similarity
between two
sequences. See, e.g., Marlin and Altschul (1993) Proc. Nat'1. Acad. Sci. USA
90:5873-5787.
One measure of similarity provided by the BLAST algorithm is the smallest sum
probability
(P(I~), which provides an indication of the probability by which a match
between two
nucleotide or amino acid sequences would occur by chance. For example, a
nucleic acid is
considered similar to a reference sequence if the smallest sum probability in
a comparison of the
test nucleic acid to the reference nucleic acid is less than about 0.2, more
preferably less than
about 0.01, and most preferably less than about 0.001. Log values may be
negative large
numbers, e.g., 5, 10, 20, 30, 40, 40, 70, 90, 110, 150, 170, etc.
An indication that two nucleic acid sequences are substantially identical is
that the
polypeptide encoded by the first nucleic acid is immunologically cross
reactive with the
antibodies raised against the polypeptide encoded by the second nucleic acid.
Thus, a
polypeptide is typically substantially identical to a second polypeptide,
e.g., where the two
peptides differ only by conservative substitutions. Another indication that
two nucleic acid
sequences are substantially identical is that the two molecules or their
complements hybridize to
each other under stringent conditions. Yet another indication that two nucleic
acid sequences
are substantially identical is that the same primers can be used to amplify
the sequences.
A "host cell" is a naturally occurnng cell or a transformed cell that contains
an
expression vector and supports the replication or expression of the expression
vector. Host cells
may be cultured cells, explants, cells in vivo, and the like. Host cells may
be prokaryotic cells
such as E. coli, or eukaryotic cells such as yeast, insect, amphibian, or
mammalian cells such as
CHO, HeLa, and the like (see, e.g., the American Type Culture Collection
catalog or web site,
www.atcc.org).
The terms "isolated," "purified," or "biologically pure" refer to material
that is
substantially or essentially free from components that normally accompany it
as found in its
native state. Purity and homogeneity are typically determined using analytical
chemistry
techniques such as polyacrylamide gel electrophoresis or high performance
liquid
chromatography. A protein or nucleic acid that is the predominant species
present in a
preparation is substantially purified. In particular, an isolated nucleic acid
is separated from
some open reading frames that naturally flank the gene and encode proteins
other than protein


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
encoded by the gene. The term "purified" in some embodiments denotes that a
nucleic acid or
protein gives rise to essentially one band in an electrophoretic gel.
Preferably, it means that the
nucleic acid or protein is at least about 85% pure, more preferably at least
95% pure, and most
preferably at least 99% pure. "Purify" or "purification" in other embodiments
means removing
at least one contaminant or component from the composition to be purified. In
this sense,
purification does not require that the purified compound be homogeneous, e.g.,
100% pure.
The terms "polypeptide," "peptide," and "protein" are used interchangeably
herein to
refer to a polymer of amino acid residues. The terms apply to amino acid
polymers in which
one or more amino acid residue is an artificial chemical mimetic of a
corresponding naturally
occurnng amino acid, as well as to naturally occurnng amino acid polymers,
those containing
modified residues, and non-naturally occurring amino acid polymers.
The term "amino acid" refers to naturally occurnng and synthetic amino acids,
as well as
amino acid analogs and amino acid mimetics that function similarly to the
naturally occurnng
amino acids. Naturally occurring amino acids are those encoded by the genetic
code, as well as
those amino acids that are later modified, e.g., hydroxyproline, 'y
carboxyglutamate, and O-
phosphoserine. Amino acid analogs refers to compounds that have the same basic
chemical
structure as a naturally occurring amino acid, e.g., an ex carbon that is
bound to a hydrogen, a
carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine,
methionine
sulfoxide, methionine methyl sulfonium. Such analogs may have modified R
groups (e.g.,
norleucine) or modified peptide backbones, but retain somebasic chemical
structure as a
naturally occurnng amino acid. Amino acid mimetic refers to a chemical
compound that has a
structure that is different from the general chemical structure of an amino
acid, but that
functions similarly to another amino acid.
Amino acids may be referred to herein by either their commonly known three
letter
symbols or by the one-letter symbols recommended by the lUPAC-IUB Biochemical
Nomenclature Commission. Nucleotides, likewise, may be referred to by their
commonly
accepted single-letter codes.
"Conservatively modified variant" applies to both amino acid and nucleic acid
sequences. With respect to particular nucleic acid sequences, conservatively
modified variants
refers to those nucleic acids which encode identical or essentially identical
amino acid
sequences, or where the nucleic acid does not encode an amino acid sequence,
to essentially
identical or associated, e.g., naturally contiguous, sequences. Because of the
degeneracy of the
11


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
genetic code, a large number of functionally identical nucleic acids encode
most proteins. For
instance, the colons GCA, GCC, GCG, and GCU each encode the amino acid
alanine. Thus, at
each position where an alanine is specified by a colon, the colon can be
altered to another of
the corresponding colons described without altering the encoded polypeptide.
Such nucleic
acid variations are "silent variations," which are one species of
conservatively modified
variations. Every nucleic acid sequence herein which encodes a polypeptide
also describes
silent variations of the nucleic acid. In certain contexts each colon in a
nucleic acid (except
AUG, which is ordinarily the only colon for methionine, and TGG, which is
ordinarily the only
colon for tryptophan) can be modified to yield a functionally similar
molecule. Accordingly, a
silent variation of a nucleic acid which encodes a polypeptide ~is implicit in
a described
sequence with respect to the expression product, but not necessarily with
respect to actual probe
sequences.
As to amino acid sequences, one of skill will recognize that individual
substitutions,
deletions, or additions to a nucleic acid, peptide, polypeptide, or protein
sequence which alters,
adds, or deletes a single amino acid or a small percentage of amino acids in
the encoded
sequence is a "conservatively modified variant" where the alteration results
in the substitution of
an amino acid with a chemically similar amino acid. Conservative substitution
tables providing
functionally similar amino acids are well known. Such conservatively modified
variants are in
addition to and do not exclude polymorphic variants, interspecies homologs,
and alleles of the
invention. Typically conservative substitutions include for one another: 1 )
Alanine (A), Glycine
(G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine
(Q); 4) Arginine
(R), Lysine (I~); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V);
6) Phenylalanine
(F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8)
Cysteine (C),
Methionine (M) (see, e.g., Creighton (1984) Proteins: Structure and Molecular
Properties
Freeman).
Macromolecular structures such as polypeptide structures can be described in
terms of
various levels of organization. For a general discussion of this organization,
see, e.g., Alberts,
et al. (eds. 2001) Molecular Biology of the Cell (4th el.) Garland; and Cantor
and Schimmel
(1980) Biophysical Chemistry Part I: The Conformation of Biological
Macromolecules
Freeman. "Primary structure" refers to the amino acid sequence of a particular
peptide.
"Secondary structure" refers to locally ordered, three dimensional structures
within a
polypeptide. These structures are commonly known as domains. Domains are
portions of a
12


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
polypeptide that often form a compact unit of the polypeptide and are
typically 25 to
approximately 500 amino acids long. Typical domains are made up of sections of
lesser
organization such as stretches of (3-sheet and a-helices. "Tertiary structure"
refers to the
complete three dimensional structure of a polypeptide monomer. "Quaternary
structure" refers
to the three dimensional structure formed, usually by the noncovalent
association of
independent tertiary units. Ariisotropic terms are also known as energy terms.
"Nucleic acid" or "oligonucleotide" or "polynucleotide" or grammatical
equivalents used
herein means at least two nucleotides covalently linked together.
Oligonucleotides are typically
from about 5, 6, 7, 8, 9, 10, 12, 15, 25, 30, 40, 50, or more nucleotides in
length, up to about
100 nucleotides in length. Nucleic acids and polynucleotides are a polymers of
any length,
including longer lengths, e.g., 200, 300, 500, 1000, 2000, 3000, 5000, 7000,
10,000, etc. A
nucleic acid of the present invention will generally contain phosphodiester
bonds, although in
some cases, nucleic acid analogs are included that may have at least one
different linkahge, e.g.,
phosphoramidate, phosphorothioate, phosphorodithioate, or O-
methylphophoroamidite linkages
(see Eckstein (1992) Oli~onucleotides and Analogues: A Practical Approach
Oxford Univ.
Press); and peptide nucleic acid backbones and linkages. Other analog nucleic
acids include
those with positive backbones; non-ionic backbones, and non-ribose backbones,
including those
described in U.S. Patent Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7 of
Sanghvi and
Cook (eds. 1994) Carbohydrate Modifications in Antisense Research ACS
Symposium Series
580. Nucleic acids containing one or more carbocyclic sugars are also included
within one
definition of nucleic acids. Modifications of the ribose-phosphate backbone
may be done for a
variety of reasons, e.g., to increase the stability and half life of such
molecules in physiological
environments or as probes on a biochip. Mixtures of naturally occurnng nucleic
acids and
analogs can be made; alternatively, mixtures of different nucleic acid
analogs, and mixtures of
naturally occurring nucleic acids and analogs may be made.
A variety of references disclose such nucleic acid analogs, including, e.g.,
phosphoramidate (Beaucage, et al. (1993) Tetrahedron 49:1925-1963 and
references therein;
Letsinger (1970) J. Or~,_Chem. 35:3800-3803; Sprinzl, et al. (1977) Eur. J.
Biochem. 81:579-
589; Letsinger, et al. (1986) Nucl. Acids Res. 14:3487-499; Sawai, et al.
(1984) Chem. Lett.
805, Letsinger, et al. (1988) J. Am. Chem. Soc. 110:4470-4471; and Pauwels, et
al. (1986)
Chemica Scripta 26:141-149), phosphorothioate (Mag, et al. (1991) Nucleic
Acids Res.
19:1437-441; and U.S. Patent No. 5,644,048), phosphorodithioate (Brill, et al.
(1989) J. Am.
13


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
Chem. Soc. 111:2321-2322), O-methylphophoroamidite linkages (see Eckstein
(1992)
Oligonucleotides and Analogues: A Practical Approach, Oxford Univ. Press), and
peptide
nucleic acid backbones and linkages (see Egholm (1992) J. Am. Chem. Soc.
114:1895-1897;
Meier, et al. (1992) Chem. Int. Ed. En~l. 31:1008-1010; Nielsen (1993) Nature
365:566-568;
Carlsson, et al. (1996) Nature 380:207, all of which are incorporated by
reference). Other
analog nucleic acids include those with positive backbones (Denpcy, et al.
(1995) Proc. Natl.
Acad. Sci. USA 92:6097-101; non-ionic backbones (U.5. Patent Nos. 5,386,023,
5,637,684,
5,602,240, 5,216,141, and 4,469,863; I~iedrowski, et al. (1991) dew. Chem.
Intl. Ed. En 1g ish
30:423-426; Letsinger, et al. (1988) J. Am. Chem. Soc. 110:4470-4471;
Letsinger, et al. (1994)
Nucleoside and Nucleotide 13:1597-xxx; Chapters 2 and 3 in Sanghvi and Cook
(eds. 1994)
Carbohydrate Modifications in Antisense Research ACS Symposium Series 580;
Mesmaeker, et
al. (1994) Bioorganic and Medicinal Chem. Lett. 4:395-398; Jeffs, et al.
(1994) J. Biomolecular
NMR 34:17; Horn, et al. (1996) Tetrahedron Lett. 37:743-xxx) and non-ribose
backbones,
including those described in U.S. Patent Nos. 5,235,033 and 5,034,506, and
Chapters 6 and T in
Sanghvi and Cook (eds. 1994) Carbohydrate Modifications in Antisense Research
ACS
Symposium Series 580. Nucleic acids containing one or more carbocyclic sugars
are also
included within one definition of nucleic acids (see Jenkins, et al. (1995)
Chem. Soc. Rev. pp
169-176). Several nucleic acid analogs are described in Rawls (page 35, June
2, 1997) C&E
News.
Particularly preferred are peptide nucleic acids (PNA) which includes peptide
nucleic
acid analogs. These backbones are substantially non-ionic under neutral
conditions, in contrast
to the highly charged phosphodiester backbone of naturally occurring nucleic
acids. This
results in at least two advantages. The PNA backbone exhibits improved
hybridization kinetics.
PNAs have larger changes in the melting temperature (Tm) for mismatched versus
perfectly
matched basepairs. DNA and RNA typically exhibit a 2-4° C drop in Tm
for an internal
mismatch. With the non-ionic PNA backbone, the drop is closer to 7-9°
C. Similarly, due to
their non-ionic nature, hybridization of the bases attached to these backbones
is relatively
insensitive to salt concentration. In addition, PNAs are not degraded by
cellular enzymes, and
thus can be more stable.
The nucleic acids may be single stranded or double stranded, as specified, or
contain
portions of both double stranded or single stranded sequence. The depiction of
a single strand
also defines the sequence of the complementary strand; thus the sequences
described herein also
14


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
provide the complement of the sequence. The nucleic acid may be DNA, both
genomic and
cDNA, RNA, or a hybrid, where the nucleic acid may contain combinations of
deoxyribo- and
ribo-nucleotides, and combinations of bases, including uracil, adenine,
thyrnine, cytosine,
guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc.
"Transcript" typically
refers to a naturally occurnng RNA, e.g., a pre-mRNA, hnRNA, or mRNA. As used
herein, the
term "nucleoside" includes nucleotides and nucleoside and nucleotide analogs,
and modified
nucleosides such as amino modified nucleosides. In addition, "nucleoside"
includes non-
naturally occurring analog structures. Thus, e.g., the individual units of a
peptide nucleic acid,
each containing a base, are referred to herein as a nucleoside.
A "label" or a "detectable moiety" is a composition detectable by
spectroscopic,
photochemical, biochemical, immunochemical, physiological, chemical, or other
physical
means. In general, labels fall into three classes: a) isotopic labels, which
may be radioactive or
heavy isotopes; b) immune labels, which may be antibodies, antigens, or
epitope tags; and c)
colored or fluorescent dyes. The labels may be incorporated into the cancer
nucleic acids,
proteins, and antibodies. For example, the label should be capable of
producing, either directly
or indirectly, a detectable signal. The detectable moiety may be a
radioisotope, such as 3H,
14C~ 32p~ 355 or 1251, electron-dense reagents, a fluorescent or
chemiluminescent compound,
such as fluorescein isothiocyanate, rhodamine, or luciferin, or an enzyme
(e.g., as commonly
used in an ELISA), biotin, digoxigenin, or haptens and proteins or other
entities which can be
made detectable such as alkaline phosphatase, beta-galactosidase, or
horseradish peroxidase.
Methods are known for conjugating the antibody to the label. See, e.g.,
Hunter, et al. (1962)
Nature 144:945; David, et al. (1974) Biochemistry 13:1014-1021; Pain, et al.
(1981) J.
Immunol. Meth. 40:219-230; and Nygren (1982) J. Histochem. and Cytochem.
30:407-412.
An "effector" or "effector moiety" or "effector component" is a molecule that
is bound
(or linked, or conjugated), either covalently, through a linker or a chemical
bond, or
noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds,
to an antibody.
The "effector" can be a variety of molecules including, e.g., detection
moieties including
radioactive compounds, fluorescent compounds, enzymes or substrates, tags such
as epitope
tags, toxins; activatable moieties, chemotherapeutic agents; lipases;
antibiotics; or radioisotopes,
e.g., emitting "hard" beta, radiation.
A "labeled nucleic acid probe or oligonucleotide" is one that is bound, e.g.,
covalently,
through a linker or a chemical bond, or noncovalently, through ionic, van der
Waals,


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
electrostatic, or hydrogen bonds to a label such that the presence of the
probe may be detected
by detecting the presence of the label bound to the probe. Alternatively,
methods using high
affinity interactions may achieve the same results where one of a pair of
binding partners binds
to the other, e.g., biotin, streptavidin.
As used herein a "nucleic acid probe or oligonucleotide" is a nucleic acid
capable of
binding to a target nucleic acid of complementary sequence through one or more
types of
chemical bonds, usually through complementary base pairing, e.g., through
hydrogen bond
formation. As used herein, a probe may include natural (e.g., A, G, C, or T)
or modified bases
(7-deazaguanosine, inosine, etc.). In addition, the bases in a probe may be
joined by a linkage
other than a phosphodiester bond, preferably one that does not functionally
interfere with
hybridization. Thus, e.g., probes may be peptide nucleic acids in which the
constituent bases
are joined by peptide bonds rather than phosphodiester linkages. Probes may
bind target
sequences lacking complete complementarity with the probe sequence depending
upon the
stringency of the hybridization conditions. The probes are preferably directly
labeled, e.g., with
isotopes, chromophores, lumiphores, chromogens, or indirectly labeled, e.g.,
with biotin to
which a streptavidin complex may later bind. By assaying for the presence or
absence of the
probe, one can detect the presence or absence of the select sequence or
subsequence. Diagnosis
or prognosis may be based at the genomic level, or at the level of RNA or
protein expression.
The term "recombinant" when used with reference, e.g., to a cell, or nucleic
acid,
protein, or vector, indicates that the cell, nucleic acid, protein, or vector,
has been modified by
the introduction of a heterologous nucleic acid or protein or the alteration
of a native nucleic
acid or protein, or that the cell is derived from a cell so modified. Thus,
e.g., recombinant cells
express genes that are not found within the native (non-recombinant) form of
the cell or express
native genes that are otherwise abnormally expressed, under expressed, or not
expressed at all.
By the term "recombinant nucleic acid" herein is meant nucleic acid,
originally formed in vitro,
in general, by the manipulation of nucleic acid, e.g., using polymerases and
endonucleases, in a
form not normally found in nature. In this manner, operably linkage of
different sequences is
achieved. Thus an isolated nucleic acid, in a linear form, or an expression
vector formed in
vitro by ligating DNA molecules that are not normally joined, are both
considered recombinant
for the purposes of this invention. It is understood that once a recombinant
nucleic acid is made
and reintroduced into a host cell or organism, it will replicate non-
recombinantly, e.g., using the
in vivo cellular machinery of the host cell rather than in vitro
manipulations; however, such
16


CA 02459219 2004-03-17
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nucleic acids, once produced recombinantly, although subsequently replicated
non
recombinantly, are still considered recombinant for the purposes of the
invention.
Similarly, a "recombinant protein" is a protein made using recombinant
techniques, e.g.,
through the expression of a recombinant nucleic acid as depicted above. A
recombinant protein
is distinguished from naturally occurring protein by at least one or more
characteristics. The
protein may be isolated or purified away from some or most of the proteins and
compounds
with which it is normally associated in its wild type host, and thus may be
substantially pure.
An isolated protein is unaccompanied by at least some of the material with
which it is normally
associated in its natural state, preferably constituting at least about 0.5%,
more preferably at
least about 5% by weight of the total protein in a given sample. A
substantially pure protein
comprises at least about 75% by weight of the total protein, with at least
about 80% being
preferred, and at least about 90% being particularly preferred. The definition
includes the
production of a skin cancer protein from one organism in a different organism
or host cell.
Alternatively, the protein may be made at a significantly higher concentration
than is normally
seen, through the use of an inducible promoter or high expression promoter,
such that the
protein is made at increased concentration levels. Alternatively, the protein
may be in a form
not normally found in nature, as in the addition of an epitope tag or amino
acid substitutions,
insertions and deletions, as discussed below.
The term "heterologous" when used with reference to portions of a nucleic acid
indicates
that the nucleic acid comprises two or more subsequences that are not normally
found in the
same relationship to each other in nature. For instance, the nucleic acid is
typically
recombinantly produced, having two or more sequences, e.g., from unrelated
genes arranged to
make a new functional nucleic acid, e.g., a promoter from one source and a
coding region from
another source. Similarly, a heterologous protein will often refer to two or
more subsequences
that are not found in the same relationship to each other in nature (e.g., a
fusion protein).
A "promoter" is typically an array of nucleic acid control sequences that
direct
transcription of a nucleic acid. As used herein, a promoter includes necessary
nucleic acid
sequences near the start site of transcription, such as, in the case of a
polymerase II type
promoter, a TATA element. A promoter also optionally includes distal enhancer
or repressor
elements, which can be located as much as several thousand base pairs from the
start site of
transcription. A "constitutive" promoter is a promoter that is active under
most environmental
and developmental conditions. An "inducible" promoter is a promoter that is
active under
17


CA 02459219 2004-03-17
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environmental or developmental regulation. The term "operably linked" refers
to a functional
linkage between a nucleic acid expression control sequence (such as a
promoter, or array of
transcription factor binding sites) and a second nucleic acid sequence, e.g.,
wherein the
expression control sequence directs transcription of the nucleic acid
corresponding to the second
sequence.
An "expression vector" is a nucleic acid construct, generated recombinantly or
synthetically, with a series of specified nucleic acid elements that permit
transcription of a
particular nucleic acid in a host cell. The expression vector can be part of a
plasmid, virus, or
nucleic acid fragment. Typically, the expression vector includes a nucleic
acid to be transcribed
in operable linkage to a promoter.
The phrase "selectively (or specifically) hybridizes to" refers to the
binding, duplexing,
or hybridizing of a molecule selectively to a particular nucleotide sequence
under stringent
hybridization conditions when that sequence is present in a complex mixture
(e.g., total cellular
or library DNA or RNA).
The phrase "stringent hybridization conditions" refers to conditions under
which a probe
will hybridize to its target subsequence, typically in a complex mixture of
nucleic acids, but to
no other sequences. Stringent conditions are sequence-dependent and will be
different in
different circumstances. Longer sequences hybridize specifically at higher
temperatures. An
extensive guide to the hybridization of nucleic acids is found in "Overview of
principles of
hybridization and the strategy of nucleic acid assays" in Tijssen (1993)
Hybridization with
Nucleic Probes (Laboratory_Techniques in Biochemistry and Molecular Biolo~y)
(vol. 24)
Elsevier. Generally, stringent conditions are selected to be about S-
10° C lower than the
thermal melting point (Tm) for the specific sequence at a defined ionic
strength pH. The Tm is
the temperature (under defined ionic strength, pH, and nucleic concentration)
at which SO% of
the probes complementary to the target hybridize to the target sequence at
equilibrium (as the
target sequences are present in excess, at Tm, 50% of the probes are occupied
at equilibrium).
Stringent conditions will be those in which the salt concentration is less
than about 1.0 M
sodium ion, typically about 0.01-1.0 M sodium ion concentration (or other
salts) at pH 7.0 to
8.3 and the temperature is at least about 30° C for short probes (e.g.,
about 10-50 nucleotides)
and at least about 60° C for long probes (e.g., greater than about 50
nucleotides). Stringent
conditions may also be achieved with the addition of destabilizing agents such
as formamide.
For selective or specific hybridization, a positive signal is typically at
least two times
18


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
background, preferably 10 times background hybridization. Exemplary stringent
hybridization
conditions can be as following: 50% formamide, Sx SSC, and 1% SDS, incubating
at 42° C, or,
Sx SSC, 1% SDS, incubating at 65° C, with wash in 0.2x SSC, and 0.1%
SDS at 65° C. For
PCR, a temperature of about 36° C is typical for low stringency
amplification, although
annealing temperatures may vary between about 32°-48° C
depending on primer length. For
high stringency PCR amplification, a temperature of about 62° C is
typical, although high
stringency annealing temperatures can range from about 50-65° C,
depending on the primer
length and specificity. Typical cycle conditions for both high and low
stringency amplifications
include a denaturation phase of 90-95° C for 30-120 sec, an annealing
phase lasting 30-120 sec,
and an extension phase of about 72° C for 1-2 min. Protocols and
guidelines for low and high
stringency amplification reactions are provided, e.g., in Innis, et al. (1990)
PCR Protocols: A
Guide to Methods and Applications, Academic Press, NY.
Nucleic acids that do not hybridize to each other under stringent conditions
are still
substantially identical if the polypeptides which they encode are
substantially identical. This
occurs, e.g.; when a copy of a nucleic acid is created using the maximum codon
degeneracy
permitted by the genetic code. In such cases, the nucleic acids typically
hybridize under
moderately stringent hybridization conditions. Exemplary "moderately stringent
hybridization
conditions" include a hybridization in a buffer of 40% formamide, 1 M NaCI, 1%
SDS at 37° C,
and a wash in 1X SSC at 45° C. A positive hybridization is typically at
least twice background.
Alternative hybridization and wash conditions can be utilized to provide
conditions of similar
stringency. Additional guidelines for determining hybridization parameters are
provided in
numerous references, e.g., Ausubel, et al. (eds. 1991 and supplements) Current
Protocols in
Molecular Biolo~y Wiley.
The phrase "functional effects" in the context of assays for testing compounds
that
modulate activity of a cancer protein includes the determination of a
parameter that is indirectly
or directly under the influence of the cancer protein or nucleic acid, e.g., a
physiological,
functional, physical, or chemical effect, such as the ability to decrease
cancer. It includes ligand
binding activity; cell viability; cell growth on soft agar; anchorage
dependence; contact
inhibition and density limitation of growth; cellular proliferation; cellular
transformation;
growth factor or serum dependence; tumor specific marker levels; invasiveness
into Matrigel;
tumor growth and metastasis in vivo; mRNA and protein expression in cells
undergoing
19


CA 02459219 2004-03-17
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metastasis; and other characteristics of cancer cells. "Functional effects"
include in vitro, in
vivo, and ex vivo activities.
By "determining the functional effect" is meant assaying for a compound that
increases
or decreases a parameter that is indirectly or directly under the influence of
a cancer protein
sequence, e.g., physiological, functional, enzymatic, physical, or chemical
effects. Such
functional effects can be measured, e:g., changes in spectroscopic
characteristics (e.g.,
fluorescence, absorbance, refractive index), hydrodynamic (e.g., shape),
chromatographic, or
solubility properties for the protein, measuring inducible markers or
transcriptional activation of
the cancer protein, measuring binding activity or binding assays, e.g.,
binding to antibodies or
other ligands, and measuring growth, cellular proliferation, cell viability,
cellular
transformation, growth factor or serum dependence, tumor specific marker
levels, invasiveness
into Matrigel, tumor growth and metastasis in vivo, mRNA and protein
expression, and other
characteristics of cancer cells. The functional effects can be evaluated by
many means, e.g.,
microscopy for quantitative or qualitative measures of alterations in
morphological features,
measurement of changes in RNA or protein levels for cancer-associated
sequences,
measurement of RNA stability, identification of downstream or reporter gene
expression (CAT,
luciferase, ~i-gal, GFP, and the like), e.g., via chemiluminescence,
fluorescence, colorimetric
reactions, antibody binding, inducible markers, and ligand binding assays.
"Inhibitors", "activators," and "modulators" of cancer polynucleotide and
polypeptide
sequences are used to refer to activating, inhibitory, or modulating molecules
or compounds
identified using in vitro and in vivo assays of cancer polynucleotide and
polypeptide sequences.
Inhibitors are compounds that, e.g., bind to, partially or totally block
activity, decrease, prevent,
delay activation, inactivate, desensitize, or down regulate the activity or
expression of cancer
proteins, e.g., antagonists. Antisense or inhibitory nucleic acids may seem to
inhibit expression
and subsequent function of the protein. "Activators" are compounds that
increase, open,
activate, facilitate, enhance activation, sensitize, agonize, or up regulate
cancer protein activity.
Inhibitors, activators, or modulators also include genetically modified
versions of cancer
proteins, e.g., versions with altered activity, as well as naturally occurring
and synthetic ligands,
antagonists, agonists, antibodies, small chemical molecules, and the like.
Such assays for
inhibitors and activators include, e.g., expressing the cancer protein in
vitro, in cells, or cell
membranes, applying putative modulator compounds, and then determining the
functional
effects on activity, as described above. Activators and inhibitors of cancer
can also be identified


CA 02459219 2004-03-17
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by incubating cancer cells with the test compound and determining increases or
decreases in the
expression of 1 or more cancer proteins, e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25,
30, 40, 50, or more
cancer proteins, such as cancer proteins encoded by the sequences set out in
Tables 1-68.
Samples or assays comprising cancer proteins that are treated with a potential
activator,
inhibitor, or modulator are compared to control samples without the inhibitor,
activator, or
modulator to examine the extent of inhibition. Control samples (untreated with
inhibitors) are
assigned a relative protein activity value of 100%. Inhibition of a
polypeptide is achieved when
the activity value relative to the control is about 80%, preferably 50%, more
preferably 25-0%.
Activation of a cancer polypeptide is achieved when the activity value
relative to the control
(untreated with activators) is 110%, more preferably 150%, more preferably 200-
500% (e.g.,
two to five fold higher relative to the control), more preferably 1000-3000%
higher.
The phrase "changes in cell growth" refers to any change in cell growth and
proliferation
characteristics in vitro or in vivo, such as cell viability, formation of
foci, anchorage
independence, semi-solid or soft agar growth, changes in contact inhibition
and density
limitation of growth, loss of growth factor or serum requirements, changes in
cell morphology,
gaining or losing immortalization, gaining or losing tumor specific markers,
ability to form or
suppress tumors when injected into suitable animal hosts, and/or
immortalization of the cell.
See, e.g., pp. 231-241 in Freshney (1994) Culture of Animal Cells a Manual of
Basic Technigue
(2d ed.) Wiley-Liss.
"Tumor cell" refers to precancerous, cancerous, and normal cells in a tumor.
"Cancer cells," "transformed" cells or "transformation" in tissue culture,
refers to
spontaneous or induced phenotypic changes that do not necessarily involve the
uptake of new
genetic material. Although transformation can arise from infection with a
transforming virus
and incorporation of new genomic DNA, or uptake of exogenous DNA, it can also
arise
spontaneously or following exposure to a carcinogen, thereby mutating an
endogenous gene.
Transformation is associated with phenotypic changes, such as immortalization
of cells,
aberrant growth control, nonmorphological changes, and/or malignancy. See,
Freshney (2000)
Culture of Animal Cells A Manual of Basic Technigue (4th ed.) Wiley-Liss.
"Antibody" refers to a polypeptide comprising a framework region from an
immunoglobulin gene or fragments thereof that specifically binds and
recognizes an antigen.
The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma,
delta, epsilon,
and mu constant region genes, as well as the myriad immunoglobulin variable
region genes.
21


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Light chains are classified as either kappa or lambda. Heavy chains are
classified as gamma,
mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes,
IgG, IgM, IgA,
IgD, and IgE, respectively. Typically, the antigen-binding region of an
antibody or its
functional equivalent will be most critical in specificity and affinity of
binding. See Paul (ed.
1999) Fundamental Immunolo~y (4th ed.) Raven.
An exerriplary immunoglobulin (antibody) structural unit comprises a tetramer.
Each
tetramer is composed of two identical pairs of polypeptide chains, each pair
having one "light"
(about 25 kD) and one "heavy" chain (about 50-70 kD). The N-terminus of each
chain defines a
variable region of about 100 to 110 or more amino acids primarily responsible
for antigen
recognition. The terms variable light chain (VL) and variable heavy chain (VH)
refer to these
light and heavy chains respectively.
Antibodies exist, e.g., as intact immunoglobulins or as a number of well-
characterized
fragments produced by digestion with various peptidases. Thus, e.g., pepsin
digests an antibody
below the disulfide linkages in the hinge region to produce F(ab)'2~ a dimer
of Fab which itself
is a light chain joined to VH-CHl by a disulfide bond. The F(ab)'2 may be
reduced under mild
conditions to break the disulfide linkage in the hinge region, thereby
converting the F(ab)'2
dimer into an Fab' monomer. The Fab' monomer is essentially Fab with part of
the hinge region
(see Paul (ed. 1999) Fundamental Immunolo~y (4th ed.) Raven. While various
antibody
fragments are defined in terms of the digestion of an intact antibody, one of
skill will appreciate
that such fragments may be synthesized de novo either chemically or by using
recombinant
DNA methodology. Thus, the term antibody, as used herein, also includes
antibody fragments
either produced by the modifieation of whole antibodies, or those synthesized
de novo using
recombinant DNA methodologies (e.g., single chain Fv) or those identified
using phage display
libraries (see, e.g., McCafferty, et al. (1990) Nature 348:552-554).
For preparation of antibodies, e.g., recombinant, monoclonal, or polyclonal
antibodies,
many techniques known. See, e.g., Kohler and Milstein (1975) Nature 256:495-
497; Kozbor, et
al. (1983) Immunology Today 4:72; Cole, et al. (1985) pp. 77-96 in Reisfeld
and Sell (1985)
Monoclonal Antibodies and Cancer Therapy Liss; Coligan (1991) Current
Protocols in
Immunolo~y Lippincott; Harlow and Lane (1988) Antibodies: A Laboratory Manual
CSH
Press; and Goding (1986) Monoclonal Antibodies: Principles and Practice (2d
ed.) Academic
Press. Techniques for the production of single chain antibodies (U.S. Patent
4,946,778) can be
adapted to produce antibodies to polypeptides of this invention. Also,
transgenic mice, or other
22


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WO 03/025138 PCT/US02/29560
organisms such as other mammals, may be used to express humanized antibodies.
Alternatively, phage display technology can be used to identify antibodies and
heteromeric Fab
fragments that specifically bind to selected antigens. See, e.g., McCafferty,
et al. (1990) Nature
348:552-554; Marks, et al. (1992) Biotechnolo~y 10:779-753.
A "chimeric antibody" is an antibody molecule in which (a) the constant
region, or a
portion thereof, is altered, replaced, or exchanged so that the antigen
binding site (variable
region) is linleed to a constant region of a different or altered class,
effector function, and/or
species, or an entirely different molecule which confers new properties to the
chimeric antibody,
e.g., an enzyme, toxin, hormone, growth factor, drug, etc.; or (b) the
variable region, or a
portion thereof, is altered, replaced, or exchanged with a variable region
having a different or
altered antigen specificity.
Identification of cancer-associated sequences
In one aspect, the expression levels of genes are determined in different
patient samples
for which diagnosis information is desired, to provide expression profiles. An
expression
profile of a particular sample is essentially a "fingerprint" of the state of
the sample; while two
states may have any particular gene similarly expressed, the evaluation of a
number of genes
simultaneously allows the generation of a gene expression profile that is
characteristic of the
state of the cell. That is, normal tissue may be distinguished from cancerous
or metastatic
cancerous tissue, or cancer tissue or metastatic cancerous tissue can be
compared with tissue
from surviving cancer patients. By comparing expression profiles of tissue in
known different
cancer states, information regarding which genes are important (including both
up-and down-
regulation of genes) in each of these states is obtained. Molecular profiling
may distinguish
subtypes of a currently collective disease designation, e.g., different forms
of a cancer.
The identification of sequences that are differentially expressed in cancer
versus non-
cancer tissue allows the use of this information in a number of ways. For
example, a particular
treatment regime may be evaluated: does a chemotherapeutic drug act to down-
regulate cancer,
and thus tumor growth or recurrence, in a particular patient. Alternatively, a
treatment step may
induce other markers which may be used as targets to destroy tumor cells.
Similarly, diagnosis
and treatment outcomes may be done or confirmed by comparing patient samples
with the
known expression profiles. Maliganant disease may be compared to non-malignant
conditions.
Metastatic tissue can also be analyzed to determine the stage of cancer in the
tissue, or origin of
primary tumor, e.g., metastasis from a remote primary site. Furthermore, these
gene expression
23


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
profiles (or individual genes) allow screening of drug candidates with an eye
to mimicking or
altering a particular expression profile; e.g., screening can be done for
drugs that suppress the
cancer expression profile. This may be done by making biochips comprising sets
of the
important cancer genes, which can then be used in these screens. These methods
can also be
done on the protein basis; that is, protein expression levels of the cancer
proteins can be
evaluated for diagnostic purposes or to screen candidate agents. In addition,
the cancer nucleic
acid sequences can be administered for gene therapy purposes, including the
administration of
antisense nucleic acids, or the cancer proteins (including antibodies and
other modulators
thereof) administered as therapeutic drugs.
Thus the present invention provides nucleic acid and protein sequences that
are
differentially expressed in cancer relative to normal tissues and/or non-
malignant disease, or in
different types of related diseases, herein termed "cancer sequences." As
outlined below, cancer
sequences include those that are up-regulated (e.g., expressed at a higher
level) in cancer, as
well as those that are down-regulated (e.g., expressed at a lower level). In a
preferred
embodiment, the cancer sequences are from humans; however, cancer sequences
from other
organisms may be useful in animal models of disease and drug evaluation; thus,
other cancer
sequences are provided, from vertebrates, including mammals, including rodents
(rats, mice,
hamsters, guinea pigs, etc.), primates, farm animals (including sheep, goats,
pigs, cows, horses,
etc.) and pets (e.g., dogs, cats, etc.). Cancer sequences from other organisms
may be obtained
using the techniques outlined below.
Cancer sequences can include both nucleic acid and amino acid sequences. In a
preferred embodiment, the skin cancer sequences are recombinant nucleic acids.
These nucleic
acid sequences are useful in a variety of applications, including diagnostic
applications, which
will detect naturally occurnng nucleic acids, as well as screening
applications; e.g., biochips
comprising nucleic acid probes or PCR microtiter plates with selected probes
to the cancer
sequences.
A cancer sequence can be initially identified by substantial nucleic acid
and/or amino
acid sequence homology to 'the cancer sequences outlined herein. Such homology
can be based
upon the overall nucleic acid or amino acid sequence, and is generally
determined as outlined
below, e.g., using homology programs or hybridization conditions.
For identifying cancer-associated sequences, the cancer screen typically
includes
comparing genes identified in different tissues, e.g., normal and cancerous
tissues, cancer and
24


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
non-malignant conditions, non-malignant conditions and normal tissues, or
tumor tissue
samples from patients who have metastatic disease vs. non metastatic tissue.
Other suitable
tissue comparisons include comparing cancer samples with metastatic cancer
samples from
other cancers, such as lung, stomach, gastrointestinal cancers, etc. Samples
of different stages
of cancer, e.g., survivor tissue, drug resistant states, and tissue undergoing
metastasis, are
applied to biochips comprising nucleic acid probes. The samples are first
microdissected, if
applicable, and treated for preparation of mRNA. Suitable biochips are
commercially available,
e.g., from Affymetrix, Santa Clara, CA. Gene expression profiles as described
herein are
generated and the data analyzed.
In one embodiment, the genes showing changes in expression as between normal
and
disease states are compared to genes expressed in other normal tissues,
including, and not
limited to lung, heart, brain, liver, stomach, kidney, muscle, colon, small
intestine, large
intestine, spleen, bone, and/or placenta. In a preferred embodiment, those
genes identified
during the cancer screen that are expressed in a significant amount in other
tissues (e.g.,
essential organs) are removed from the profile, although in some embodiments,
this is not
necessary (e.g., where organs may be dispensible, e.g., female or male
specific). That is, when
screening for drugs, it is usually preferable that the target expression be
disease specific, to
minimize possible side effects on other organs were there expression.
In a preferred embodiment, cancer sequences are those that are up-regulated in
cancer;
that is, the expression of these genes is higher in the cancer tissue as
compared to non-cancer or
non-malignant tissue. "Up-regulation" as used herein often means at least
about a two-fold
change, preferably at least about a three fold change, with at least about
five-fold or higher
being preferred. Another embodiment is directed to sequences up-regulated in
non-malignant
conditions relative to normal. Uniformity among relevant samples is also
preferred.
Unigene cluster identification numbers and accession numbers herein are for
the
GenBank sequence database and the sequences of the accession numbers are
hereby expressly
incorporated by reference. GenBank is available, see, e.g., Benson, et al.
(1998) Nuc. Acids
Res. 26:1-7; and http://www.ncbi.nlm.nih.gov/. Sequences are also available in
other databases,
e.g., European Molecular Biology Laboratory (EMBL) and DNA Database of Japan
(DDBJ).
In some situations, the sequences may be derived from assembly of available
sequences or be
predicted from genomic DNA using exon prediction algorithms, such as FGENESH.
See


CA 02459219 2004-03-17
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Salamov and Solovyev (2000) Genome Res. 10:516-522. In other situations,
sequences have
been derived from cloning and sequencing of isolated nucleic acids.
In another preferred embodiment, cancer sequences are those that are down-
regulated in
the cancer; that is, the expression of these genes is lower in cancer tissue
as compared to non-
cancerous tissue. "Down-regulation" as used herein often means at least about
a two-fold
change, preferably at least about a three fold change, with at least about
five-fold or higher
being preferred.
Informatics
The ability to identify genes that axe over or under expressed in cancer can
additionally
provide high-resolution, high-sensitivity datasets which can be used in the
areas of diagnostics,
therapeutics, drug development, pharmacogenetics, protein structure, biosensor
development,
and other related areas. For example, the expression profiles can be used in
diagnostic or
prognostic evaluation of patients with cancer or related diseases. See Tables
1 and 3. Or as
another example, subcellular toxicological information can be generated to
better direct drug
structure and activity correlation (see Anderson (June 11-12, 1998)
Pharmaceutical Proteomics:
Targets Mechanism, and Function, paper presented at the IBC Proteomics
conference,
Coronado, CA). Subcellular toxicological information can also be utilized in a
biological
sensor device to predict the likely toxicological effect of chemical exposures
and likely tolerable
exposure thresholds (see U.S. Patent No. 5,811,231). Similar advantages accrue
from datasets
relevant to other biomolecules and bioactive agents (e.g., nucleic acids,
saccharides, lipids,
drugs, and the like).
Thus, in another embodiment, the present invention provides a database that
includes at
least one set of assay data. The data contained in the database is acquired,
e.g., using array
analysis either singly or in a library format. The database can be in a form
in which data can be
maintained and transmitted, but is preferably an electronic database. The
electronic database of
the invention can be maintained on any electronic device allowing for the
storage of and access
to the database, such as a personal computer, but is preferably distributed on
a wide area
network, such as the World Wide Web.
The focus of the present section on databases that include peptide sequence
data is for
clarity of illustration only. Similar databases can be assembled for assay
data acquired using an
assay of the invention.
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The compositions and methods for identifying andlor quantitating the relative
and/or
absolute abundance of a variety of molecular and macromolecular species from a
biological
sample representing cancer, e.g., the identification of cancer-associated
sequences described
herein, provide an abundance of information which can be correlated with
pathological
conditions, predisposition to disease, drug testing, therapeutic monitoring,
gene-disease causal
linkages, identification of correlates of immunity and physiological status,
among others.
Although the data generated from the assays of the invention is suited for
manual review and
analysis, in a preferred embodiment, data processing using high-speed
computers is utilized.
An array of methods for indexing and retrieving biomolecular information is
available.
For example, U.S. Patents 6,023,659 and 5,966,712 disclose a relational
database~system for
storing biomolecular sequence information in a manner that allows sequences to
be catalogued
and searched according to one or more protein function hierarchies. U.S.
Patent 5,953,727
discloses a relational database having sequence records containing information
in a format that
allows a collection of partial-length DNA sequences to be catalogued and
searched according to
association with one or more sequencing projects for obtaining full-length
sequences from the
collection of partial length sequences. U.S. Patent 5,706,498 discloses a gene
database retrieval
system for making a retrieval of a gene sequence similar to a sequence data
item in a gene
database based on the degree of similarity between a key sequence and a target
sequence. U.S:
Patent 5,538,897 discloses a method using mass spectroscopy fragmentation
patterns of
peptides to identify amino acid sequences in computer databases by comparison
of predicted
mass spectra with experimentally-derived mass spectra using a closeness-of fit
measure. U.S.
Patent 5,926,818 discloses a mufti-dimensional database comprising a
functionality for multi-
dimensional data analysis described as on-line analytical processing (OLAP),
which entails the
consolidation of projected and actual data according to more than one
consolidation path or
dimension. U.S. Patent 5,295,261 reports a hybrid database structure in which
the fields of each
database record are divided into two classes, navigational and informational
data, with
navigational fields stored in a hierarchical topological map which can be
viewed as a tree
structure or as the merger of two or more such tree structures. See also
Baxevanis, et al. (2001)
Bioinformatics: A Practical Guuide to the Analysis of Genes and Proteins
Wiley; Mount (2001)
Bioinformatics: Sequence and Genome Analysis CSH Press, NY; Durbin, et al.
(eds. 1999)
Biological Sequence Ana~sis: Probabilistic Models of Proteins and Nucleic
Acids Cambridge
University Press; Baxevanis and Oeullette (eds. 1998) Bioinformatics: A
Practical Guide to the
27


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
Analysis of Genes and Proteins (2d. ed.) Wiley-Liss; Rashidi and Buehler
(1999)
Bioinformatics: Basic Applications in Biological Science and Medicine CRC
Press; Setubal, et
al. (eds. 1997) Introduction to Computational Molecular Biolo~y Brooks/Cole;
Misener and
Krawetz (eds. 2000) Bioinformatics: Methods and Protocols Humana Press;
Higgins and Taylor
S (eds. 2000) Bioinformatics: Sequence Structure, and Databanks: A Practical
Approach Oxford
University Press; Brown (2001) Bioinformatics: A Biologist's Guide to
Biocomputing and the
Internet Eaton Pub.; Han and I~amber (2000) Data Mining: Concepts and
Techniques
I~aufinann Pub.; and Waterman (1995) Introduction to Computational Biology:
Maps
Sequences, and Genomes Chap and Hall.
The present invention provides a computer database comprising a computer and
software for storing in computer-retrievable form assay data records cross-
tabulated, e.g., with
data specifying the source of the target-containing sample from which each
sequence specificity
record was obtained.
In an exemplary embodiment, at least one of the sources of target-containing
sample is
from a control tissue sample known to be free of pathological disorders. In a
variation, at least
one of the sources is a known pathological tissue specimen, e.g., a neoplastic
lesion or another
tissue specimen to be analyzed for cancer. In another variation, the assay
records cross-tabulate
one or more of the following parameters for each target species in a sample:
(1) a unique
identification code, which can include, e.g., a target molecular structure
and/or characteristic
separation coordinate (e.g., electrophoretic coordinates); (2) sample source;
and (3) absolute
and/or relative quantity of the target species present in the sample.
The invention also provides for the storage and retrieval of a collection of
target data in
a computer data storage apparatus, which can include magnetic disks, optical
disks, magneto-
optical disks, DRAM, SRAM, SGRAM, SDRAM, RDRAM, DDR RAM, magnetic bubble
memory devices, and other data storage devices, including CPU registers and on-
CPU data
storage arrays. Typically, the target data records are stored as a bit pattern
in an array of
magnetic domains on a magnetizable medium or as an array of charge states or
transistor gate
states, such as an array of cells in a DRAM device (e.g., each cell comprised
of a transistor and
a charge storage area, which may be on the transistor). In one embodiment, the
invention
provides such storage devices, and computer systems built therewith,
comprising a bit pattern
encoding a protein expression fingerprint record comprising unique identifiers
for at least 10
target data records cross-tabulated with target source.
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CA 02459219 2004-03-17
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When the target is a peptide or nucleic acid, the invention preferably
provides a method
for identifying related peptide or nucleic acid sequences, comprising
performing a computerized
comparison between a peptide or nucleic acid sequence assay record stored in
or retrieved from
a computer storage device or database and at least one other sequence. The
comparison can
include a sequence analysis or comparison algorithm or computer program
embodiment thereof
(e.g., FASTA, TFASTA, GAP, BESTFIT) and/or the comparison may be of the
relative amount
of a peptide or nucleic acid sequence in a pool of sequences determined from a
polypeptide or
nucleic acid sample of a specimen.
The invention also preferably provides a magnetic disk, such as an IBM-
compatible
(DOS, Windows, Windows95/98/2000, Windows NT, OS/2) or other format (e.g.,
Linux,
SunOS, Solaris, AIX, SCO Unix, VMS, MV, Macintosh, etc.) floppy diskette or
hard (fixed,
Winchester) disk drive, comprising a bit pattern encoding data from an assay
of the invention in
a file format suitable for retrieval and processing in a computerized sequence
analysis,
comparison, or relative quantitation method.
The invention also provides a network, comprising a plurality of computing
devices
linked via a data link, such as an Ethernet cable (coax or lOBaseT), telephone
line, ISDN line,
wireless network, optical fiber, or other suitable signal transmission medium,
whereby at least
one network device (e.g., computer, disk array, etc.) comprises a pattern of
magnetic domains
(e.g., magnetic disk) and/or charge domains (e.g., an array of DRAM cells)
composing a bit
pattern encoding data acquired from an assay of the invention.
The invention also provides a method for transmitting assay data that includes
generating an electronic signal on an electronic communications device, such
as a modem,
ISDN terminal adapter, DSL, cable modem, ATM switch, or the like, wherein the
signal
includes (in native or encrypted format) a bit pattern encoding data from an
assay or a database
comprising a plurality of assay results obtained by the method of the
invention.
In a preferred embodiment, the invention provides a computer system for
comparing a
query target to a database containing an array of data structures, such as an
assay result obtained
by the method of the invention, and ranking database targets based on the
degree of identity and
gap weight to the target data. A central processor is preferably initialized
to load and execute
the computer program for alignment and/or comparison of the assay results.
Data for a query
target is entered into the central processor via an I/O device. Execution of
the computer
29


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
program results in the central processor retrieving the assay data from the
data file, which
comprises a binary description of an assay result.
The target data or record and the computer program can be transferred to
secondary
memory, which is typically random access memory (e.g., DRAM, SRAM, SGRAM, or
SDRAM). Targets are ranked according to the degree of correspondence between a
selected
assay characteristic (e.g., binding to a selected affinity moiety) and the
same characteristic of
the query target and results are output via an UO device. For example, a
central processor can
be a conventional computer (e.g., Intel Pentium, PowerPC, Alpha, PA-8000,
SPARC, MIPS
4400, M1PS 10000, VAX, etc.); a program can be a commercial or public domain
molecular
biology software package (e.g., UWGCG Sequence Analysis Softwaxe, Darwin); a
data file can
be an optical or magnetic disk, a data server, a memory device (e.g., DRAM,
SRAM, SGRAM,
SDRAM, EPROM, bubble memory, flash memory, etc.); an I/O device can be a
terminal
comprising a video display and a keyboard, a modem, an ISDN terminal adapter,
an Ethernet
port, a punched card reader, a magnetic strip reader, or other suitable I/O
device.
The invention also preferably provides the use of a computer system, such as
that
described above, which comprises: (1) a computer; (2) a stored bit pattern
encoding a collection
of peptide sequence specificity records obtained by the methods of the
invention, which may be
stored in the computer; (3) a comparison target, such as a query target; and
(4) a program for
alignment and comparison, typically with rank-ordering of comparison results
on the basis of
computed similarity values. See, e.g., Ewens and Grant (2001) Statistical
Methods in
Bioinformatics: An Introduction Springer-Verlag. Mathematical approaches can
also be used to
conclude whether similarities or differences in the gene expression exhibited
by different
samples are significant. See, e.g., Golub, et al. (1999) Science 286:531-537;
Duda, et al. (2001)
Pattern Classification Wiley; and Hastie, et al. (2001) The Elements of
Statistical Learning:
Data Mining Inference, and Prediction Springer-Verlag. One approach to
determine whether a
sample is more similar to or has maximum similarity with a given condition
between the sample
and one or more pools representing different conditions for comparison; the
pool with the
smallest vector angle is then chosen as the most similar to the biological
sample among the
pools compared.
Characteristics of cancer-associated proteins
Cancer proteins of the present invention may be classified as secreted
proteins,
transmembrane proteins, or intracellular proteins. In one embodiment, the
cancer protein is an


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
intracellular protein. Intracellular proteins may be found in the cytoplasm
and/or in the nucleus.
Intracellular proteins are involved in all aspects of cellular function and
replication (including,
e.g., signaling pathways); aberrant expression of such proteins often results
in unregulated or
disregulated cellular processes (see, e.g., Alberts, et al. (eds. 1994)
Molecular Biolo~;y of the
Cell (3d ed.) Garland). For example, many intracellular proteins have
enzymatic activity such
as protein kinase activity, protein phosphatase activity, protease activity,
nucleotide cyclase
activity, polymerase activity, and the like. Intracellular proteins also serve
as docking proteins
that are involved in organizing complexes of proteins, or targeting proteins
to various
subcellular localizations, and are involved in maintaining the structural
integrity of organelles.
An increasingly appreciated concept in characterizing proteins is the presence
in the
proteins of one or more structural motifs for which defined functions have
been attributed. In
addition to the highly conserved sequences found in the enzymatic domain of
proteins, highly
conserved sequences have been identified in proteins that are involved in
protein-protein
interaction. For example, Src-homology-2 (SH2) domains bind tyrosine-
phosphorylated targets
in a sequence dependent manner. PTB domains, which are distinct from SH2
domains, also
bind tyrosine phosphorylated targets. SH3 domains bind to proline-rich
targets. In addition, PH
domains, tetratricopeptide repeats and WD domains to name only a few, have
been shown to
mediate protein-protein interactions. Some of these may also be involved in
binding to
phospholipids or other second messengers. These motifs can be identified on
the basis of amino
acid sequence; thus, an analysis of the sequence of proteins may provide
insight into both the
enzymatic potential of the molecule and/or molecules with which the protein
may associate.
One useful database is Pfam (protein families), which is a large collection of
multiple sequence
alignments and hidden Markov models covering many common protein domains.
Versions are
available via the Internet from Washington University in St. Louis, the Sanger
Center in
England, and the Karolinska Institute in Sweden. See, e.g., Bateman, et al.
(2000) Nuc. Acids
Res. 28:263-266; Sonnhammer, et al. (1997) Proteins 28:405-420 ; Bateman, et
al. (1999) Nuc.
Acids Res. 27:260-262; and Sonnhammer, et al. (1998) Nuc. Acids Res. 26:320-
322.
In another embodiment, the cancer sequences are transmembrane proteins.
Transmembrane proteins are molecules that span a phospholipid bilayer of a
cell. They may
have an intracellular domain, an extracellular domain, or both. The
intracellular domains of
such proteins may have a number of functions including those already described
for
intracellular proteins. For example, the intracellular domain may have
enzymatic activity
31


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and/or may serve as a binding site for additional proteins. Frequently the
intracellular domain
of transmembrane proteins serves both roles. For example certain receptor
tyrosine kinases
have both protein kinase activity and SH2 domains. In addition,
autophosphorylation of
tyrosines on the receptor molecule itself, creates binding sites for
additional SH2 domain
containing proteins.
Transmembrane proteins may contain from one to many transmembrane domains. For
example, receptor tyrosine kinases, certain cytokine receptors, receptor
guanylyl cyclases and
receptor serine/threonine protein kinases contain a single transmembrane
domain. However,
various other proteins including channels and adenylyl cyclases contain
numerous
transmembrane domains. Many important cell surface receptors such as G protein
coupled
receptors (GPCRs) are classified as "seven transmembrane domain" proteins, as
they contain 7
membrane spanning regions. Characteristics of transmembrane domains include
approximately
17 consecutive hydrophobic amino acids that may be followed by charged amino
acids.
Therefore, upon analysis of the amino acid sequence of a particular protein,
the localization and
number of transmembrane domains within the protein may be predicted (see,
e.g., PSORT web
site http://psort.nibb.ac.jpn. Important transmembrane protein receptors
include, but are not
limited to the insulin receptor, insulin-like growth factor receptor, human
growth hormone
receptor, glucose transporters, transferrin receptor, epidermal growth factor
receptor, low
density lipoprotein receptor, epidermal growth factor receptor, leptin
receptor, and interleukin
receptors, e.g., IL-1 receptor, IL-2 receptor, etc.
The extracellular domains of transmembrane proteins are diverse; however,
conserved
motifs are found repeatedly among various extracellular domains. Conserved
structure and/or
functions have been ascribed to different extracellular motifs. Many
extracellular domains are
involved in binding to other molecules. In one aspect, extracellular domains
are found on
receptors. Factors that bind the receptor domain include circulating ligands,
which may be
peptides, proteins, or small molecules such as adenosine and the like. For
example, growth
factors such as EGF, FGF, and PDGF are circulating growth factors that bind to
their cognate
receptors to initiate a variety of cellular responses. Other factors include
cytokines, mitogenic
factors, neurotrophic factors, and the like. Extracellular domains also bind
to cell-associated
molecules. In this respect, they may mediate cell-cell interactions. Cell-
associated ligands can
be tethered to the cell, e.g., via a glycosylphosphatidylinositol (GPI)
anchor, or may themselves
32


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be transmembrane proteins. Extracellular domains may also associate with the
extracellular
matrix and contribute to the maintenance of the cell structure.
Cancer proteins that are transmembrane are particularly preferred in the
present
invention as they are readily accessible targets for immunotherapeutics, as
are described herein.
In addition, as outlined below, transmembrane proteins can be also useful in
imaging
modalities. Antibodies may be used to label such readily accessible proteins
in situ.
Alternatively, antibodies can also label intracellular proteins, in which case
samples are
typically permeablized to provide access to intracellular proteins. In
addition, some membrane
proteins can be processed to release a soluble protein, or to expose a
residual fragment.
Released soluble proteins may be useful diagnostic markers, processed residual
protein
fragments may be useful lung markers of disease.
It will also be appreciated that a transmembrane protein can be made soluble
by
removing transmembrane sequences, e.g., through recombinant methods.
Furthermore,
transmembrane proteins that have been made soluble can be made to be secreted
through
recombinant means by adding an appropriate signal sequence.
In another embodiment, the cancer proteins are secreted proteins; the
secretion of which
can be either constitutive or regulated. These proteins may have a signal
peptide or signal
sequence that targets the molecule to the secretory pathway. Secreted proteins
are involved in
numerous physiological events; e.g., if circulating, they often serve to
transmit signals to
various other cell types. The secreted protein may function in an autocrine
manner (acting on
the cell that secreted the factor), a paracrine manner (acting on cells in
close proximity to the
cell that secreted the factor), an endocrine manner (acting on cells at a
distance, e.g, secretion
into the blood stream), or exocrine (secretion, e.g., through a duct or to
adjacent epithelial
surface as sweat glands, sebaceous glands, pancreatic ducts, lacrimal glands,
mammary glands,
wax producing glands of the ear, etc.). Thus secreted molecules often find use
in modulating or
altering numerous aspects of physiology. Cancer proteins that are secreted
proteins are
particularly preferred in the present invention as they serve as good targets
for diagnostic
markers, e.g., for blood, plasma, serum, or stool tests. Those which are
enzymes may be
antibody or small molecule targets. Others may be useful as vaccine targets,
e.g., via CTL
mechanisms.
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Use of cancer nucleic acids
As described above, cancer sequence is initially identified by substantial
nucleic acid
and/or amino acid sequence homology or linkage to the cancer sequences
outlined herein. Such
homology can be based upon the overall nucleic acid or amino acid sequence,
and is generally
determined as outlined below, using either homology programs or hybridization
conditions.
Typically, linked sequences on a mRNA are found on the same molecule.
As detailed elsewhere, percent identity can be determined using an algorithm
such as
BLAST. A preferred method utilizes the BLASTN module of WU-BLAST-2 set to the
default
parameters, with overlap span and overlap fraction set to 1 and 0.125,
respectively. Alignment
may include the introduction of gaps in the sequences to be aligned. In
addition, for sequences
which contain either more or fewer nucleotides than those of the nucleic acids
described, the
percentage of homology may be determined based on the number of homologous
nucleosides in
relation to the total number of nucleosides. Thus, e.g., homology of sequences
shorter than
those of the sequences identified will be determined using the number of
nucleosides in the
shorter sequence.
In one embodiment, the nucleic acid homology is determined through
hybridization
studies. Thus, e.g., nucleic acids which hybridize under high stringency to a
described nucleic
acid, or its complement, or is also found on naturally occurnng mRNAs is
considered a cancer
sequence. In another embodiment, less stringent hybridization conditions are
used; e.g.,
moderate or low stringency conditions may be used; see Ausubel, supra, and
Tijssen, supra.
The cancer nucleic acid sequences of the invention, e.g., the sequences in
Tables 1-68,
can be fragments of larger genes, e.g., they are nucleic acid segments.
"Genes" in this context
includes coding regions, non-coding regions, and mixtures of coding and non-
coding regions.
Accordingly, using the sequences provided herein, extended sequences, in
either direction, of
the cancer genes can be obtained, using techniques well known for cloning
either longer
sequences or the full length sequences; see Ausubel, et al., supra. Much can
be done by
informatics and many sequences can be clustered to include multiple sequences
corresponding
to a single gene, e.g., systems such as UniGene (see,
http://www.ncbi.nlm.nih.gov/UniGene/).
Once a cancer nucleic acid is identified, it can be cloned and, if necessary,
its constituent
parts recombined to form the entire cancer nucleic acid coding regions or the
entire mRNA
sequence. Once isolated from its natural source, e.g., contained within a
plasmid or other vector
or excised therefrom as a linear nucleic acid segment, the recombinant cancer
nucleic acid can
34


CA 02459219 2004-03-17
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be further used as a probe to identify and isolate other cancer nucleic acids,
e.g., extended
coding regions. It can also be used as a "precursor" nucleic acid to make
modified or variant
cancer nucleic acids and proteins.
The cancer nucleic acids of the present invention are used in several ways. In
one
embodiment, nucleic acid probes to the cancer nucleic acids are made and
attached to biochips
to be used in screening and diagnostic methods, as outlined below, or for
administration, e.g.,
for gene therapy, vaccine, RNAi, and/or antisense applications. Alternatively,
cancer nucleic
acids that include coding regions of cancer proteins can be put into
expression vectors for the
expression of cancer proteins, again for screening purposes or for
administration to a patient.
In a preferred embodiment, nucleic acid probes to cancer nucleic acids (both
the nucleic
acid sequences outlined in the figures and/or the complements thereof) are
made. The nucleic
acid probes attached to the biochip are designed to be substantially
complementary to the cancer
nucleic acids, e.g., the target sequence (either the target sequence of the
sample or to other
probe sequences, e.g., in sandwich assays), such that hybridization of the
target sequence and
~ the probes of the present invention occurs. As outlined below, this
complementarity need not
be perfect; there may be any number of base pair mismatches which will
interfere with
hybridization between the target sequence and the single stranded nucleic
acids of the present
invention. However, if the number of mutations is so great that no
hybridization can occur
under even the least stringent of hybridization conditions, the sequence is
not a complementary
target sequence. Thus, by "substantially complementary" herein is meant that
the probes are
sufficiently complementary to the target sequences to hybridize under normal
reaction
conditions, particularly high stringency conditions, as outlined herein.
A nucleic acid probe is generally single stranded but can be partially single
and partially
double stranded. The strandedness of the probe is dictated by the structure,
composition, and
properties of the target sequence. In general,~the nucleic acid probes range
from about 8-100
bases long, with from about 10-80 bases being preferred, and from about 30-50
bases being
particularly preferred. That is, generally whole genes are not used. In some
embodiments,
much longer nucleic acids can be used, up to hundreds of bases.
In a preferred embodiment, more than one probe per sequence is used, with
either
overlapping probes or probes to different sections of the target being used.
That is, two, three,
four or more probes, with three being preferred, are used to build in a
redundancy for a


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
particular target. The probes can be overlapping (e.g., have some sequence in
common), or
separate. In some cases, PCR primers may be used to amplify signal for higher
sensitivity.
Nucleic acids can be attached or immobilized to a solid support in a wide
variety of
ways. By "immobilized" and grammatical equivalents herein is meant the
association or
binding between the nucleic acid probe and the solid support is sufficient to
be stable under the
conditions of binding, washing, analysis, and removal as outlined. The binding
can typically be
covalent or non-covalent. By "non-covalent binding" and grammatical
equivalents herein is
meant one or more of electrostatic, hydrophilic, and hydrophobic interactions.
Included in non-
covalent binding is the covalent attachment of a molecule, e.g., streptavidin
to the support and
the non-covalent binding of the biotinylated probe to the streptavidin. By
"covalent binding"
and grammatical equivalents herein is meant that the two moieties, the solid
support and the
probe, are attached by at least one bond, including sigma bonds, pi bonds, and
coordination
bonds. Covalent bonds can be formed directly between the probe and the solid
support or can
be formed by a cross linker or by inclusion of a specific reactive group on
either the solid
support or the probe or both molecules. Immobilization may also involve a
combination of
covalent and non-covalent interactions.
In general, the probes are attached to the biochip in a wide variety of ways.
As
described herein, the nucleic acids can either be synthesized first, with
subsequent attachment to
the biochip, or can be directly synthesized on the biochip.
The biochip comprises a suitable solid substrate. By "substrate" or "solid
support" or
- other grammatical equivalents herein is meant a material that can be
modified for the
attachment or association of the nucleic acid probes and is amenable to at
least one detection
method. Often, the substrate may contain discrete individual sites appropriate
for individual
partitioning and identification. The number of possible substrates is very
large, and include, but
are not limited to, glass and modified or functionalized glass, plastics
(including acrylics,
polystyrene and copolymers of styrene and other materials, polypropylene,
polyethylene,
polybutylene, polyurethanes, TeflonJ, etc.), polysaccharides, nylon or
nitrocellulose, resins,
silica or silica-based materials including silicon and modified silicon,
carbon, metals, inorganic
glasses, plastics, etc. In general, the substrates allow optical detection and
do not appreciably
fluoresce. See WO 0055627.
Generally the substrate is planar, although other configurations of substrates
may be
used as well. For example, the probes may be placed on the inside surface of a
tube for flow-
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CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
through sample analysis to minimize sample volume. Similarly, the substrate
may be flexible,
such as a flexible foam, including closed cell foams made of particular
plastics.
In a preferred embodiment, the surface of the biochip and the probe may be
derivatized
with chemical functional groups for subsequent attachment of the two. Thus,
e.g., the biochip is
derivatized with a chemical functional group including, but not limited to,
amino groups,
carboxy groups, oxo groups, and thiol groups, with amino groups being
particularly preferred.
Using these functional groups, the probes can be attached using functional
groups on the probes.
For example, nucleic acids containing amino groups can be attached to surfaces
comprising
amino groups, e.g., using linkers; e.g., homo-or hetero-bifunctional linkers
as are well known
(see 1994 Pierce Chemical Company catalog, technical section on cross-linkers,
pages 155-
200). In addition, in some cases, additional linkers, such as alkyl groups
(including substituted
and heteroalkyl groups) may be used.
In this embodiment, oligonucleotides are synthesized, and then attached to the
surface of
the solid support. Either the S' or 3' terminus may be attached to the solid
support, or
attachment may be via linkage to an internal nucleoside. In another
embodiment, the
immobilization to the solid support may be very strong, yet non-covalent. For
example,
biotinylated oligonucleotides can be made, which bind to surfaces covalently
coated with
streptavidin, resulting in attachment.
Alternatively, the oligonucleotides may be synthesized on the surface. For
example,
photoactivation techniques utilizing photopolymerization compounds and
techniques are used.
In a preferred embodiment, the nucleic acids can be synthesized in situ, using
known
photolithographic techniques, such as those described in WO 95/25116; WO
95/35505; U.S.
Patent Nos. 5,700,637 and 5,445,934; and references cited within, all of which
are expressly
incorporated by reference; these methods of attachment form the basis of the
Affymetrix
GeneChipTM technology.
Often, amplification-based assays are performed to measure the expression
level of
cancer-associated sequences. These assays are typically performed in
conjunction with reverse
transcription. In such assays, a cancer-associated nucleic acid sequence acts
as a template in an
amplification reaction (e.g., Polymerase Chain Reaction, or PCR). In a
quantitative
amplification, the amount of amplification product will be proportional to the
amount of
template in the original sample. Comparison to appropriate controls provides a
measure of the
amount of cancer-associated RNA. Methods of quantitative amplification are
well known.
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Detailed protocols for quantitative PCR are provided, e.g., in Innis, et al.
(1990) PCR Protocols,
A Guide to Methods and Applications Academic Press.
In some embodiments, a TaqMan based assay is used to measure expression.
TaqMan
based assays use a fluorogenic oligonucleotide probe that contains a 5'
fluorescent dye and a 3'
quenching agent. The probe hybridizes to a PCR product, but cannot itself be
extended due to a
blocking agent at the 3' end. When the PCR product is amplified in subsequent
cycles, the 5'
nuclease activity of the polymerase, e.g., AmpliTaq, results in the cleavage
of the TaqMan
probe. This cleavage separates the 5' fluorescent dye and the 3' quenching
agent, thereby
resulting in an increase in fluorescence as a function of amplification (see,
e.g., literature
provided by Perkin-Elmer, e.g., www2.perkin-elmer.com).
Other suitable amplification methods include, but are not limited to, ligase
chain
reaction (LCR) (see Wu and Wallace (1989) Genomics 4:560-569, Landegren, et
al. (1988)
Science 241:1077-1080, and Barnnger, et al. (1990) Gene 89:117-122),
transcription
amplification (Kwoh, et al. (1989) Proc. Natl. Acad. Sci. USA 86:1173-1177),
self sustained
sequence replication (Guatelli, et al. (1990) Proc. Nat. Acad. Sci. USA
87:1874-1878), dot
PCR, linker adapter PCR, etc.
Expression of cancer proteins from nucleic acids
In a preferred embodiment, cancer nucleic acids, e.g., encoding cancer
proteins, are used
to make a variety of expression vectors to express cancer proteins which can
then be used in
screening assays, as described below. Expression vectors and recombinant DNA
technology are
-well known (see, e.g., Ausubel, supra, and Fernandez and Hoeffler (eds. 1999)
Gene Expression
S sS terns Academic Press) to express proteins. The expression vectors may be
either self
replicating extrachromosomal vectors or vectors which integrate into a host
genome. Generally,
these expression vectors include transcriptional and translational regulatory
nucleic acid
operably linked to the nucleic acid encoding the cancer protein. The term
"control sequences"
refers to DNA sequences used for the expression of an operably linked coding
sequence in a
particular host organism. Control sequences that are suitable for prokaryotes,
e.g., include a
promoter, optionally an operator sequence, and a ribosome binding site.
Eukaryotic cells are
known to utilize promoters, polyadenylation signals, and enhancers.
Nucleic acid is "operably linked" when it is placed into a functional
relationship with
another nucleic acid sequence. For example, DNA for a presequence or secretory
leader is
operably linked to DNA for a polypeptide if it is expressed as a preprotein
that participates in
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CA 02459219 2004-03-17
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the secretion of the polypeptide; a promoter or enhancer is operably linked to
a coding sequence
if it affects the transcription of the sequence; or a ribosome binding site is
operably linked to a
coding sequence if it is positioned so as to facilitate translation.
Generally, "operably linked"
means that the DNA sequences being linked are contiguous, and, in the case of
a secretory
S leader, contiguous and in reading phase. However, enhancers do not have to
be contiguous.
Linking is typically accomplished by ligation at convenient restriction sites.
If such sites do not
exist, synthetic oligonucleotide adaptors or linkers are used in accordance
with conventional
practice. Transcriptional and translational regulatory nucleic acid will
generally be appropriate
to the host cell used to express the cancer protein. Numerous types of
appropriate expression
vectors and suitable regulatory sequences are known for a variety of host
cells.
In general, transcriptional and translational regulatory sequences may
include, but are
not limited to, promoter sequences, ribosomal binding sites, transcriptiorial
start and stop
sequences, translational start and stop sequences, and enhancer or activator
sequences. In a
preferred embodiment, the regulatory sequences include a promoter and
transcriptional start and
1 S stop sequences.
Promoter sequences may be either constitutive or inducible promoters. The
promoters
may be either naturally occurring promoters or hybrid promoters. Hybrid
promoters, which
combine elements of more than one promoter, are also known, and are useful in
the present
invention.
An expression vector may comprise additional elements. For example, the
expression
vector may have two replication systems, thus allowing it to be maintained in
two organisms,
e.g., in mammalian or insect cells for expression and in a prokaryotic host
for cloning and
amplification. Furthermore, for integrating expression vectors, the expression
vector often
contains at least one sequence homologous to the host cell genome, and
preferably two
homologous sequences which flank the expression construct. The integrating
vector may be
directed to a specific locus in the, host cell by selecting the appropriate
homologous sequence
for inclusion in the vector. Constructs for integrating vectors are available.
See, e.g.,
Fernandez and Hoeffler, supra; and Kitamura, et al. (1995) Proc. Nat'1 Acad.
Sci. USA 92:9146-
9150.
In addition, in a preferred embodiment, the expression vector contains a
selectable
marker gene to allow the selection of transformed host cells. Selection genes
are well known
and will vary with the host cell used.
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The cancer proteins of the present invention are usually produced by culturing
a host cell
transformed with an expression vector containing nucleic acid encoding a
cancer protein, under
the appropriate conditions to induce or cause expression of the cancer
protein. Conditions
appropriate for cancer protein expression will vary with the choice of the
expression vector and
the host cell, and will be easily ascertained through routine experimentation
or optimization.
For example, the use of constitutive promoters in the expression vector will
require optimizing
the growth and proliferation of the host cell, while the use of an inducible
promoter requires the
appropriate growth conditions for induction. In addition, in some embodiments,
the timing of
the harvest is important. For example, the baculoviral systems used in insect
cell expression are
lytic viruses, and thus harvest time selection can be crucial for product
yield.
Appropriate host cells include yeast, bacteria, archaebacteria, fungi, and
insect and
animal cells, including mammalian cells. Of particular interest are
Saccharomyces cerevisiae
and other yeasts, E. coli, Bacillus subtilis, Sf~3 cells, C129 cells, 293
cells, Neurospora, BHK,
CHO, COS, HeLa cells, HLJVEC (human umbilical vein endothelial cells), THP1
cells (a
macrophage cell line), and various other human cells and cell lines.
In a preferred embodiment, the cancer proteins are expressed in mammalian
cells.
Mammalian expression systems may be used, and include retroviral and
adenoviral systems.
One expression vector system is a retroviral vector system such as is
generally described in
PCT/LJS97/01019 and PCT/US97/01048. Of particular use as mammalian promoters
are the
promoters from mammalian viral genes, since the viral genes are often highly
expressed and
have a broad host range. Examples include the SV40 early promoter, mouse
mammary tumor
virus LTR promoter, adenovirus major late promoter, herpes simplex virus
promoter, and the
CMV promoter (see, e.g., Fernandez and Hoeffler, supra). Typically,
transcription termination
and polyadenylation sequences recognized by mammalian cells are regulatory
regions located 3'
to the translation stop codon and thus, together with the promoter elements,
flank the coding
sequence. Examples of transcription terminator and polyadenlyation signals
include those
derived from SV40.
Methods of introducing exogenous nucleic acid into mammalian hosts, as well as
other
hosts, are available, and will vary with the host cell used. Techniques
include dextran-mediated
transfection, calcium phosphate precipitation, polybrene mediated
transfection, protoplast
fusion, electroporation, viral infection, encapsulation of the
polynucleotide(s) in liposomes, and
direct microinjection of the DNA into nuclei.


CA 02459219 2004-03-17
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In a preferred embodiment, cancer proteins are expressed in bacterial systems.
Promoters from bacteriophage may also be used. In addition, synthetic
promoters and hybrid
promoters are also useful; e.g., the tac promoter is a hybrid of the trp and
lac promoter
sequences. Furthermore, a bacterial promoter can include naturally occurnng
promoters of non-
bacterial origin that have the ability to bind bacterial RNA polymerase and
initiate transcription.
In addition to a functioning promoter sequence, an efficient ribosome binding
site is desirable.
The expression vector may also include a signal peptide sequence that provides
for secretion of
the cancer protein in bacteria. The protein is either secreted into the growth
media (gram-
positive bacteria) or into the periplasmic space, located between the inner
and outer membrane
of the cell (gram-negative bacteria). The bacterial expression vector may also
include a
selectable marker gene to allow for the selection of bacterial strains that
have been transformed.
Suitable selection genes include genes which render the bacteria resistant to
drugs such as
ampicillin, chloramphenicol, erythromycin, kanamycin, neomycin, and
tetracycline. Selectable
markers also include biosynthetic genes, such as those in the histidine,
tryptophan, and leucine
biosynthetic pathways. These components are assembled into expression vectors.
Expression
vectors for bacteria are well known, and include vectors for Bacillus
subtilis, E. coli,
Streptococcus cremoris, and Streptococcus lividans, among others (e.g.,
Fernandez and
Hoeffler, supra). The bacterial expression vectors are transformed into
bacterial host cells using
techniques such as calcium chloride treatment, electroporation, and others.
In one embodiment, cancer proteins axe produced in insect cells using, e.g.,
expression
vectors forthe transformation of insect cells, and in particular, baculovirus-
based expression
vectors.
In a preferred embodiment, a cancer protein is produced in yeast cells. Yeast
expression
systems are well known, and include expression vectors for Saccharomyces
cerevisiae, Candida
albicans and C. maltosa, Hansenula polymorpha, Kluyveromyces fragilis and K.
lactis, Pichia
guillerimondii and P. pastoris, Schizosaccharomyces pombe, and Yarrowia
lipolytica.
The cancer protein may also be made as a fusion protein, using available
techniques.
Thus, e.g., for the creation of monoclonal antibodies, if the desired epitope
is small, the cancer
protein may be fused to a carrier protein to form an immunogen. Alternatively,
the cancer
protein may be made as a fusion protein to increase expression, or for other
reasons. For
example, when the cancer protein is a cancer peptide, the nucleic acid
encoding the peptide may
41


CA 02459219 2004-03-17
n
r.
G~ ;:.t '
(;:;" sa ",~ It ~ -~ ~~; ~ '' ,.fit. t( .~t~ tF '_ : ~~MA :i ;' ~' I "',iA? ~
t~e .~~ 1~ t ' ~~~' I :' i
~,./~_."
be linked to other nucleic acid for expression purposes. Fusion with detection
epitope tags can
be made, e.g., with FLAG, His6 (SEQ,.II? NO:409), myc, HA, etc.
Tn a preferred embodiment, the cancer protein is purified or isolated after
expression. .
Cancer proteins may be isolated or purified in a variety of ways depending on
what other
components are present in the sample and the requirements for purified
product, e.g., natural
conformation or denatured. Standard purification methods include ammonium
sulfate
precipitations, electrophoretic, molecular, immunological, and chromatographic
techniques,
including ion exchange, hydrophobic, affinity, and reverse-phase HPLC
chromatography, and
chromatofocusing. For example, the cancer protein may be purified using a
standard anti-
cancer protein antibody column. Ultraf ltration and diafiltration techniques,
in conjunction with .
protein concentration, are also useful. See, e.g., Walsh (2002) Proteins:
Biochemistry and
Biotechnolo~y Wiley; Hardin, et al. (eds. 2001) Cloning, Gene Expression and
Protein
Purification Oxford Univ. Press; Wilson, et al. (eds. 2000) Encyclopedia of
Separation Science
Academic Press; and Scopes (1993) Protein Purification Springer-Verlag. The
degree of
purification necessary will vary depending on the use of the cancer protein.
In some instances
no purification will be necessary.
Once expres~ed and purified if necessary, the cancer proteins and nucleic
acids are
useful in a number of applications. They may be used as immunoselection
reagents, as vaccine
reagents, as screening agents, therapeutic entities, for production of
antibodies, as transcription
or translation inhibitors, etc.
Variants of cancer proteins
Also included within one embodiment of cancer proteins are amino acid variants
of the
naturally occurring sequences, as determined herein. Preferably, the variants
are preferably
greater than about 75% homologous to the wild-type sequence, more preferably
greater than
about 80%, even more preferably greater than about 85%, and most preferably
greater than
90%. In some embodiments the homology will be as high as about 93-95% or 98%.
As for
nucleic acids, homology in this context means sequence similarity or identity,
with identity
being preferred. This homology will be determined using standard techniques,
as are outlined
above for nucleic acid homologies.
Cancer proteins of the present invention may be shorter or longer than the
wild type
amino acid sequences. Thus, in a preferred embodiment, included within the
definition of
42


CA 02459219 2004-03-17
'~ ~n~ v'y,y, ~ ~~ ~Jl~.~V
cancer proteins are portions or fragments of the wild type sequences herein.
In addition, as
P
i
%~
42a


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
outlined above, the cancer nucleic acids of the invention may be used to
obtain additional
coding regions, and thus additional protein sequence.
In one embodiment, the cancer proteins are derivative or variant cancer
proteins as
compared to the wild-type sequence. That is, as outlined more fully below, the
derivative
S cancer peptide will often contain at least one amino acid substitution,
deletion, or insertion, with
amino acid substitutions being particularly preferred. The amino acid
substitution, insertion, or
deletion may occur at many residue positions within the cancer peptide.
Also included within one embodiment of cancer proteins of the present
invention are
amino acid sequence variants. These variants typically fall into one or more
of three classes:
substitutional, insertional, or deletional variants. These variants ordinarily
are prepared by site
specific mutagenesis of nucleotides in the DNA encoding the cancer protein,
using cassette or
PCR mutagenesis or other techniques, to produce DNA encoding the variant, and
thereafter
expressing the DNA in recombinant cell culture as outlined above. However,
variant cancer
protein fragments having up to about 100-150 residues may be prepared by in
vitro'synthesis
using established techniques. Amino acid sequence variants are characterized
by the
predetermined nature of the variation, a feature that sets them apart from
naturally occurring
allelic or interspecies variation of the cancer protein amino acid sequence.
The variants
typically exhibit a similar qualitative biological activity as a naturally
occurnng analogue,
although variants can also be selected which have modified characteristics.
While the site or region fox introducing an amino acid sequence variation is
often
predetermined, the mutation per se need not be predetermined. For example, in
order to
optimize the performance of a mutation at a given site, random mutagenesis may
be conducted
at the target codon or region and the expressed cancer variants screened for
the optimal
combination of desired activity. Techniques for making substitution mutations
at predetermined
sites in DNA having a known sequence are well known, e.g., M13 primer
mutagenesis and PCR
mutagenesis. Screening of mutants is often done using assays of cancer protein
activities.
Amino acid substitutions are typically of single residues; insertions usually
will be on
the order of from about 1-20 amino acids, although considerably larger
insertions may be
tolerated. Deletions generally range from about 1-20 residues, although in
some cases deletions
may be much larger.
Substitutions, deletions, insertions, or combination thereof may be used to
arnve at a
final derivative. Generally these changes are done on a few amino acids to
minimize the
43


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
alteration of the molecule. However, larger changes may be tolerated in
certain circumstances.
When small alterations in the characteristics of the cancer protein are
desired, substitutions are
generally made in accordance with the amino acid substitution relationships
described.
The variants typically exhibit essentially the same qualitative biological
activity and will
elicit the same immune response as a naturally-occurring analog, although
variants also are
selected to modify the characteristics of cancer proteins as needed.
Alternatively, the variant
may be designed such that a biological activity of the cancer protein is
altered. For example,
glycosylation sites may be added, altered, or removed.
Substantial changes in function or immunological identity are sometimes made
by
selecting substitutions that are less conservative than those described above.
For example,
substitutions may be made which more significantly affect: the structure of
the polypeptide
backbone in the area of the alteration, for example the alpha-helical or beta-
sheet structure; the
charge or hydrophobicity of the molecule at the target site; or the bulk of
the side chain.
Substitutions which generally are expected to produce the greatest changes in
the polypeptide's
properties are those in which (a) a hydrophilic residue, e.g., serine or
threone is substituted for
(or by) a hydrophobic residue, e.g., leucine, isoleucine, phenylalanine,
valine, or alanine; (b) a
cysteine or proline is substituted for (or by) another residue; (c) a residue
having an
electropositive side chain, e.g., lysine, arginine, or histidine, is
substituted for (or by) an
electronegative residue, e.g., glutamic or aspartic acid; (d) a residue having
a bulky side chain,
e.g., phenylalanine, is substituted for (or by) one not having a side chain,
e.g., glycine; or (e) a
proline residue is incorporated or substituted, which changes the degree of
rotational freedom of
the peptidyl bond.
Variants typically exhibit a similar qualitative biological activity and will
elicit the same
immune response as the naturally-occurring analog, although variants also are
selected to
modify the characteristics of the skin cancer proteins as needed.
Alternatively, the variant may
be designed such that the biological activity of the cancer protein is
altered. For example,
glycosylation sites may be altered or removed.
Covalent modifications of cancer polypeptides are included within the scope of
this
invention. One type of covalent modification includes reacting targeted amino
acid residues of
a cancer polypeptide with an organic derivatizing agent that is capable of
reacting with selected
side chains or the N-or C-terminal residues of a cancer polypeptide.
Derivatization with
bifunctional agents is useful, for instance, for crosslinking cancer
polypeptides to a water-
44


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
insoluble support matrix or surface for use in a method for purifying anti-
cancer polypeptide
antibodies or screening assays, as is more fully described below. Commonly
used crosslinking
agents include, e.g., l,l-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-
hydroxysuccinimide esters, e.g., esters with 4-azidosalicylic acid,
homobifunctional
imidoesters, including disuccinimidyl esters such as 3,3'-
dithiobis(succinimidylpropionate),
bifurictional maleimides such as bis-N-maleimido-1,8-octane and agents such as
methyl-3-((p-
azidophenyl)dithio)propioimidate.
Other modifications include deamidation of glutaminyl and asparaginyl residues
to the
corresponding glutamyl and aspartyl residues, respectively, hydroxylation of
proline and lysine,
phosphorylation of hydroxyl groups of serinyl, threonyl, or tyrosyl residues,
methylation of the
amino groups of the lysine, arginine, and histidine side chains (e.g., pp. 79-
86, Creighton (1992)
Proteins: Structure and Molecular Pro ep rties Freeman), acetylation of the N-
terminal amine,
and amidation of a C-terminal carboxyl group.
Another type of covalent modification of the cancer polypeptide included
within the
scope of this invention comprises altering the native glycosylation pattern of
the polypeptide.
"Altering the native glycosylation pattern" is intended for purposes herein to
mean deleting one
or more carbohydrate moieties found in native sequence cancer polypeptide,
and/or adding one
or more glycosylation sites that are not present in the native sequence cancer
polypeptide.
Glycosylation patterns can be altered in many ways. Different cell types to
express cancer-
associated sequences can result in different glycosylation patterns.
Addition of glycosylation sites to cancer polypeptides may also be
accomplished by
altering the amino acid sequence thereof. The alteration may be made, e.g., by
the addition of,
or substitution by, one or more serine or threonine residues to the native
sequence cancer
polypeptide (for O-linked glycosylation sites). The cancer amino acid sequence
may optionally
be altered through changes at the DNA level, particularly by mutating the DNA
encoding the
cancer polypeptide at preselected bases such that codons are generated that
will translate into
the desired amino acids.
Another means of increasing the number of carbohydrate moieties on the cancer
polypeptide is by chemical or enzymatic coupling of glycosides to the
polypeptide. See, e.g.,
WO 87/05330; pp. 259-306 in Aplin and Wriston (I981) CRC Crit. Rev. Biochem.
Removal of carbohydrate moieties present on the cancer polypeptide may be
accomplished chemically or enzymatically or by mutational substitution of
codons encoding for


CA 02459219 2004-03-17
._ .. ' . ~~.~,~...~,..~.. .' ~ ~ ~'7 m~ ~, y ..,; ,.... ,,... , ,~. ~."'41~.
.,~..;~,;~., ....,~
~ ~ : 1~ 1~"y;t>y _ : ~rwk.ta'~: . ( '~~ ~~~ ~~'~~~~~'~Ns~ .::b
amino acid residues that serve as targets for glycosylation. Chemical
de~3ycosylation
techniques are applicable; See, e.g., Sojax and Bahl (1987) Arch. Biochem.
Biophys. 259:52-57
and Edge, et al. (1981) Anal. Bioch~m. 118:131-137. Enzymatic cleavage of
carbohydrate
moieties on polypeptides can be achieved by tla~ i~~a variety of endo-and exo-
glycosidases.
S See, e.g., Thotakura, et al. (1987) Meth. Enzymol. 138:350-359.
Another type of covalent modification of cancer comprises linking the cancer
polypeptide to one of a variety of nonproteinaceous polymers, e.g.,
polyethylene glycol,
polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U.S.
Patent Nos.
4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192, or4,179,337.
I O Cancer polypeptides of the present invention may also be modified in a way
to form
chimeric molecules comprising a cancer polypeptide fused to another
heterologous polypeptide
or amino acid sequence. In one embodiment, such a chimeric molecule comprises
a fusion of a
'cancer polypeptide with a tag polypeptide which provides an epitope to which
an anti-tag ,
antibody can selectively bind. The epitope.tag is generally placed at the
amino-or carboxyl-
1 S terminus of the cancer polypeptide. The presence of such epitope-tagged
forms of a cancer
polypeptide can be detected using an antibody against the tag polypeptide.
Also, provision of
the epitope tag enables the cancer polypeptide to be readily purified by
affinity purification
using an anti-tag antibody or another type of affinity matrix that binds to
the epitope tag. In an
alternative embodiment, the chimeric molecule may comprise a fusion of a
cancer polypeptide
20 with an immunoglobulin or a particular region of an immunoglobulin. For a
bivalent form of
the chimeric molecule, such a fusion could be to the Fc region of an IgG
molecule.
Various tag polypeptides and their respective antibodies are available.
Examples
include poly-histidine (poly-his) or poly-histidine-glycine (poly-his-gly)
tags; His6 (SEQ ID
N0:409) and metal chelation tags, the flu HA tag polypeptide and its antibody
12CAS (Field, et
2S al. (1988) Mol. Cell. Biol. 8:2159-2165); the c-myc tag and the 8F9, 3C7,
6E10, G4, B7, and
9EI0 antibodies thereto (Evan, et al. (1985) Molecular and Cellular Biology
5:3610-3616); and
the Herpes Simplex virus glycoprotein D (gD) tag and its antibody (Paborsky,
et al. (1990)
Protein Engineering 3(6):547-553). Other tag polypeptides include the Flag-
peptide (Hopp, et
al. (1988) BioTechnologv 6:1204-1210); the KT3 epitope peptide (Martin, et al.
(1992) Science
30 255:192-194); tubulin epitope peptide (Skinner, et al. (1991) J. Biol.
Chem. 266:15163-15166);
,46


CA 02459219 2004-03-17
r:;;.' t~..' ..,'~..'1 ' n~.~ ~..".i< l~;,j~ u~ ' , ' ~ sr~'~ ~;.;Ej-'x~,." :
~f~.;. ~t'~',~ t'~ "'T ~ . ,'t:.'".':~ ~ ~". ' ~°ij .,: is
~.._
u,~:;:~:~,
~_~ ...w:::
".
and the T7 gene 10 protein peptide tag (Lutz-Freyermuth, et al. (1990) Proc:
Natl. Acad. Sci.
USA 87:6393-63~~7).
e~,~3 .
~6a
,r . ..-,nre~ !fAl.p ~i~


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
Also included are other cancer proteins of the cancer family, and cancer
proteins from
other organisms, which are cloned and expressed as outlined below. Thus, probe
or degenerate
polymerase chain reaction (PCR) primer sequences may be used to find other
related cancer
proteins from humans or other organisms. Particularly useful probe andlor PCR
primer
S sequences include the unique areas of the cancer nucleic acid sequence.
Preferred PCR primers
are from about 15-35 nucleotides in length, with from about 20-30 being
preferred, and may
contain inosine as needed. The conditions for PCR reaction have been well
described (e.g.,
Innis, PCR Protocols, supra).
In addition, cancer proteins can be made that are longer than those encoded by
the
nucleic acids of the Tables, e.g., by the elucidation of extended sequences,
the addition of
epitope or purification tags, the addition of other fusion sequences, etc.
Cancer proteins may also be identified as being encoded by cancer nucleic
acids. Thus,
cancer proteins are encoded by nucleic acids that will hybridize to the
sequences of the
sequence listings, or their complements, as outlined herein.
Antibodies to cancer proteins
In a preferred embodiment, when the cancer protein is to be used to generate
antibodies,
e.g., for immunotherapy or immunodiagnosis, the cancer protein should share at
least one
epitope or determinant with the full length protein. By "epitope" or
"determinant" herein is
typically meant a portion of a protein which will generate and/or bind an
antibody or T-cell
receptor in the context of MHC. Thus, in most instances, antibodies made to a
smaller cancer
protein will be able to bind to the full-length protein, particularly linear
epitopes. In a preferred
embodiment, the epitope is unique; that is, antibodies generated to a unique
epitope show little
or no cross-reactivity. In a preferred embodiment, the epitope is selected
from a protein
sequence set out in the tables.
Methods of preparing polyclonal antibodies exist (e.g., Coligan, supra; and
Harlow and
Lane, supra). Polyclonal antibodies can be raised in a mammal, e.g., by one or
more injections
of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing
agent and/or
adjuvant will be injected in the mammal by multiple subcutaneous or
intraperitoneal injections.
The immunizing agent may include a protein encoded by a nucleic acid of Tables
1-68 or
fragment thereof or a fusion protein thereof. It may be useful to conjugate
the immunizing
agent to a protein known to be immunogenic in the mammal being immunized.
Examples of
such immunogenic proteins include but are not limited to keyhole limpet
hemocyanin, serum
47


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Examples of
adjuvants which
may be employed include Freund's complete adjuvant and MPL-TDM adjuvant
(monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). Various
immunization
protocols may be used.
The antibodies may, alternatively, be monoclonal antibodies. Monoclonal
antibodies
maybe prepared using hybridoma methods, such as those described by I~ohler and
Milstein
(1975) Nature 256:495. In a hybridoma method, a mouse, hamster, or other
appropriate host
animal, is typically immunized with an immunizing agent to elicit lymphocytes
that produce or
are capable of producing antibodies that will specifically bind to the
immunizing agent.
Alternatively, the lymphocytes may be immunized in vitro. The immunizing agent
will
typically include a polypeptide encoded by a nucleic acid of the tables or
fragment thereof, or a
fusion protein thereof. Generally, either peripheral blood lymphocytes
("PBLs") are used if
cells of human origin are desired, or spleen cells or lymph node cells are
used if non-human
mammalian sources are desired. The lymphocytes are then fused with an
immortalized cell line
using a suitable fusing agent, such as polyethylene glycol, to form a
hybridoma cell (e.g., pp.
59-103 in Goding (1986) Monoclonal Antibodies: Principles and Practice
Academic Press).
Immortalized cell lines are usually transformed mammalian cells, particularly
myeloma cells of
rodent, bovine, or human origin. Usually, rat or mouse myeloma cell lines are
employed. The
hybridoma cells may be cultured in a suitable culture medium that preferably
contains one or
more substances that inhibit the growth or survival of the unfused,
immortalized cells. For
example, if the parental cells lack the enzyme hypoxanthine guanine
phosphoribosyl transferase
(HGPRT or HPRT), the culture medium for the hybridomas typically will include
hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances
prevent the
growth of HGPRT-deficient cells.
In one embodiment, the antibodies are bispecific antibodies. Bispecific
antibodies are
monoclonal, preferably human or humanized, antibodies that have binding
specificities for at
least two different antigens or that have binding specificities for two
epitopes on the same
antigen. In one embodiment, one of the binding specificities is for a protein
encoded by a
nucleic acid of the tables or a fragment thereof, the other one is for another
antigen, and
preferably for a cell-surface protein or receptor or receptor subunit,
preferably one that is tumor
specific. Alternatively, tetramer-type technology may create multivalent
reagents.
48


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
In a preferred embodiment, the antibodies to cancer protein are capable of
reducing or
eliminating a biological function of a cancer protein, in a naked form or
conjugated to an
effector moiety, as is described below. That is, the addition of anti-cancer
protein antibodies
(either polyclonal or preferably monoclonal) to cancer tissue (or cells
containing cancer) may
reduce or eliminate the cancer. Generally, at least a 25% decrease in
activity, growth, size, or
the like is preferred, with at Ieast about 50% being particularly preferred
and about a 95-100%
decrease being especially preferred.
In a preferred embodiment the antibodies to the cancer proteins are humanized
antibodies (e.g., Xenerex Biosciences, Medarex, Inc., Abgenix, Inc., Protein
Design Labs, Inc.)
Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules
of
immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab,
Fab', F(ab')2
or other antigen-binding subsequences of antibodies) which contain minimal
sequence derived
from non-human immunoglobulin. Humanized antibodies include human
immunoglobulins
(recipient antibody) in which residues from a complementary determining region
(CDR) of the
1 S recipient are replaced by residues from a CDR of a non-human species
(donor antibody) such as
mouse, rat, or rabbit having the desired specificity, affinity, and capacity.
In some instances, Fv
framework residues of a human immunoglobulin are replaced by corresponding non-
human
residues. Humanized antibodies may also comprise residues which are found
neither in the
recipient antibody nor in the imported CDR or framework sequences. In general,
a humanized
antibody will comprise substantially all of at Ieast one, and typically two,
variable domains, in
which all or substantially all of the CDR regions correspond to those of a non-
human
immunoglobulin and all or substantially alI of the framework (FR) regions are
those of a human
immunoglobulin consensus sequence. The humanized antibody optimally also will
typically
comprise at least a portion of an immunoglobulin constant region (Fc),
typically that of a human
immunoglobulin (Jones, et al. (1986) Nature 321:522-525; Riechmann, et al.
(1988) Nature
332:323-329; and Presta (1992) Cunr. Op. Struct. Biol. 2:593-596).
Humanization can be
essentially performed following the method of Winter and co-workers (Jones, et
al. (1986)
Nature 321:522-525; Riechmann, et al. (1988) Nature 332:323-327; Verhoeyen, et
al. (1988)
Science 239:1534-1536), by substituting rodent CDRs or CDR sequences for
corresponding
sequences of a human antibody. Accordingly, such humanized antibodies are
chimeric
antibodies (LJ.S. Patent No. 4,816,567), wherein substantially less than an
intact human variable
domain has been substituted by corresponding sequence from a non-human
species.
49


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
Human antibodies can also be produced using phage display libraries
(Hoogenboom and
Winter (1992) J. Mol. Biol. 227:381-388; Marks, et al. (1991) J. Mol. Biol.
222:581-597) or
human monoclonal antibodies (e.g., p. 77, Cole, et al. in Reisfeld and Sell
(1985) Monoclonal
Antibodies and Cancer Therapy Liss; and Boerner, et al. (1991) J. Immunol.
147:86-95).
Similarly, human antibodies can be made by introducing human immunoglobulin
loci into
transgenic animals, e.g., mice in which the endogenous immunoglobulin genes
have been
partially or completely inactivated. Upon challenge, human antibody production
is observed,
which closely resembles that seen in humans in nearly all respects, including
gene
rearrangement, assembly, and antibody repertoire. This approach is described,
e.g., in U.S.
Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016,
and in the
following scientific publications: Marks, et al. (1992) Bio/Technolo~y 10:779-
783; Lonberg, et
al. (1994) Nature 368:856-859; Mornson (1994) Nature 368:812-13; Fishwild, et
al. (1996)
Nature Biotechnolo~y 14:845-851; Neuberger (1996) Nature Biotechnolo~y 14:826;
and
Lonberg and Huszar (1995) Intern. Rev. lmmunol. 13:65-93.
By immunotherapy is meant treatment of cancer with an antibody raised against
cancer
proteins. As used herein, immunotherapy can be passive or active. Passive
immunotherapy as
defined herein is the passive transfer of antibody to a recipient (patient).
Active immunization
is the induction of antibody and/or T-cell responses in a recipient (patient).
Induction of an
immune response is the result of providing the recipient with an antigen to
which antibodies are
raised. The antigen may be provided by injecting a polypeptide against which
antibodies are
desired to be raised into a recipient, or contacting the recipient with a
nucleic acid capable of
expressing the antigen and under conditions for expression of the antigen,
leading to an immune
response.
In a preferred embodiment the cancer proteins against which antibodies are
raised are
secreted proteins as described above. Without being bound by theory,
antibodies used for
treatment may bind and prevent the secreted protein from binding to its
receptor, thereby
inactivating the secreted cancer protein, e.g., in autocrine signaling.
In another preferred embodiment, the cancer protein to which antibodies are
raised is a
transmembrane protein. Without being bound by theory, antibodies used for
treatment may
bind the extracellular domain of the cancer protein and prevent it from
binding to other proteins,
such as circulating ligands or cell-associated molecules. The antibody may
cause down-
regulation of the transmembrane cancer protein. The antibody may be a
competitive, non-


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
competitive or uncompetitive inhibitor of protein binding to the extracellular
domain of the
cancer protein. The antibody may also be an antagonist of the cancer protein.
Further, the
antibody may prevent activation of the transmembrane cancer protein, or may
induce or
suppress a particular cellular pathway. In one aspect, when the antibody
prevents the binding of
other molecules to the cancer protein, the antibody prevents growth of the
cell. The antibody
may also be used to target or sensitize the cell to cytotoxic agents,
including, but not limited to
TNF-a, TNF-(3, IL-1, INF-y, and IL-2, or chemotherapeutic agents including
SFU, vinblastine,
actinomycin D, cisplatin, methotrexate, and the like. In some instances the
antibody may
belong to a sub-type that activates serum complement when complexed with the
transmembrane
protein thereby mediating cytotoxicity or antigen-dependent cytotoxicity
(ADCC). Thus,
cancer may be treated by administering to a patient antibodies directed
against the
transmembrane cancer protein. Antibody-labeling may activate a co-toxin,
localize a toxin
payload, or otherwise provide means to locally ablate cells.
In another preferred embodiment, the antibody is conjugated to an effector
moiety. The
effector moiety can be various molecules, including labeling moieties such as
radioactive labels
or fluorescent labels, or can be a therapeutic moiety. In one aspect the
therapeutic moiety is a
small molecule that modulates the activity of a cancer protein. In another
aspect the therapeutic
moiety may modulate the activity of molecules associated with or in close
proximity to a cancer
protein. The therapeutic moiety may inhibit enzymatic or signaling activity
such as protease or
collagenase or protein kinase activity associated with cancer, or be an
attractant of other cells,
such as NK cells.
In a preferred embodiment, the therapeutic moiety can also be a cytotoxic
agent. In this
method, targeting the cytotoxic agent to cancer tissue or cells results in a
reduction in the
number of afflicted cells, thereby reducing symptoms associated with cancer.
Cytotoxic agents
are numerous and varied and include, but are not limited to, cytotoxic drugs
or toxins or active
fragments of such toxins. Suitable toxins and their corresponding fragments
include diphtheria
A chain, exotoxin A chain, ricin A chain, abrin A chain, curcin, croon,
phenomycin, enomycin,
saporin, auristatin, and the like. Gytotoxic agents also include
radiochemicals made by
conjugating radioisotopes to antibodies raised against cancer proteins, or
binding of a
radionuclide to a chelating agent that has been covalently attached to the
antibody. Targeting
the therapeutic moiety to transmembrane cancer proteins not only serves to
increase the local
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concentration of therapeutic moiety in the cancer afflicted area, but also
serves to reduce
deleterious side effects that may be associated with the untargeted
therapeutic moiety.
In another preferred embodiment, the cancer protein against which the
antibodies are
raised is an intracellular protein. In this case, the antibody may be
conjugated to a protein
which facilitates entry into the cell. In one case, the antibody enters the
cell by endocytosis. In
another embodiment, a nucleic acid encoding the antibody is administered to
the individual or
cell. Moreover, wherein the cancer protein can be targeted within a cell,
e.g., the nucleus, an
antibody thereto may contain a signal for that target localization, e.g., a
nuclear localization
signal.
The cancer antibodies of the invention specifically bind to cancer proteins.
By
"specifically bind" herein is meant that the antibodies bind to the protein
with a I~ of at least
about 0.1 mM, more usually at least about 1 ~,M, preferably at least about 0.1
~.M or better, and
most preferably, 0.01 ~,M or better. Selectivity of binding to the specific
target and not to
related sequences is often also important.
Detection of cancer sequence for diagnostic and therapeutic applications
In one aspect, the RNA expression levels of genes are determined for different
cellular
states in the cancer phenotype. Expression levels of genes in normal tissue
(e.g., not
undergoing cancer) and in cancer tissue (and in some cases, for varying
severities of cancer that
relate to prognosis, as outlined below), or in non-malignant disease are
evaluated to provide
expression profiles. A gene expression profile of a particular cell state or
point of development
is essentially a "fingerprint" of the state of the cell. While two states may
have a particular gene
similarly expressed, the evaluation of a number of genes simultaneously allows
the generation
of a gene expression profile that is reflective of the state of the cell. By
comparing expression
profiles of cells in different states, information regarding which genes are
important (including
both up- and down-regulation of genes) in each of these states is obtained.
Then, diagnosis may
be performed or confirmed to determine whether a tissue sample has the gene
expression profile
of normal or cancerous tissue. This will provide for molecular diagnosis of
related conditions.
"Differential expression," or grammatical equivalents as used herein, refers
to qualitative
or quantitative differences in the temporal and/or cellular gene expression
patterns within and
among cells and tissue. Thus, a differentially expressed gene can
qualitatively have its
expression altered, including an activation or inactivation, in, e.g., normal
versus cancer tissue.
Genes may be turned on or turned off in a particular state, relative to
another state thus
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permitting comparison of two or more states. A qualitatively regulated gene
will exhibit an
expression pattern within a state or cell type which is detectable by standard
techniques. Some
genes will be expressed in one state or cell type, but not in both.
Alternatively, the difference in
expression may be quantitative, e.g., in that expression is increased or
decreased; e.g., gene
expression is either upregulated, resulting in an increased amount of
transcript, or
downregulated, resulting in a decreased amount of transcript. The degree to
which expression
differs need only be large enough to quantify via standard characterization
techniques as
outlined below, such as by use of Affymetrix GeneChipTM expression arrays.
See, Lockhart
(1996) Nature Biotechnology 14:1675-1680. Other techniques include, but are
not limited to,
quantitative reverse transcriptase PCR, northern analysis, and RNase
protection. As outlined
above, preferably the change in expression (e.g., upregulation or
downregulation) is at least
about 50%, more preferably at least about 100%, more preferably at least about
150%, more
preferably at least about 200%, with from 300 to at least 1000% being
especially preferred.
Evaluation may be at the gene transcript or the protein level. The amount of
gene
expression may be monitored using nucleic acid probes to the RNA or DNA
equivalent of the
gene transcript, and the quantification of gene expression levels, or,
alternatively, the final gene
product itself (protein) can be monitored, e.g., with antibodies to the cancer
protein and standard
immunoassays (ELISAs, etc.) or other techniques, including mass spectroscopy
assays, 2D gel
electrophoresis assays, etc. Proteins corresponding to cancer genes, e.g.,
those identified as
being important in a cancer or disease phenotype, can be evaluated in a cancer
diagnostic test.
In a preferred embodiment, gene expression monitoring is performed
simultaneously on a
number of genes. Multiple protein expression monitoring can be performed as
well.
In this embodiment, the cancer nucleic acid probes are attached to biochips as
outlined
herein for the detection and quantification of cancer sequences in a
particular cell. The assays
are further described below in the example. PCR techniques can be used to
provide greater
sensitivity.
In a preferred embodiment nucleic acids encoding the cancer protein are
detected.
Although DNA or RNA encoding the cancer protein may be detected, of particular
interest are
methods wherein anlmRNA encoding a cancer protein is detected. Probes to
detect mRNA can
be a nucleotideldeoxynucleotide probe that is complementary to and hybridizes
with the mRNA
and includes, but is not limited to, oligonucleotides, cDNA, or RNA. Probes
also should
contain a detectable label, as defined herein. In one method the mRNA is
detected after
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immobilizing the nucleic acid to be examined on a solid support such as nylon
membranes and
hybridizing the probe with the sample. Following washing to remove the non-
specifically
bound probe, the label is detected. In another method, detection of the mRNA
is performed in
situ. In this method permeabilized cells or tissue samples are contacted with
a detectably
labeled nucleic acid probe for sufficient time to allow the probe to hybridize
with the target
mRNA. Following washing to remove the non-specifically bound probe, the label
is detected.
For example a digoxygenin labeled riboprobe (RNA probe) that is complementary
to the mRNA
encoding a cancer protein is detected by binding the digoxygenin with an anti-
digoxygenin
secondary antibody and developed with nitro blue tetrazolium and 5-bromo-4-
chloro-3-indoyl
phosphate.
In a preferred embodiment, various proteins from the three classes of proteins
as
described herein (secreted, transmembrane, or intracellular proteins) are used
in diagnostic
assays. The cancer proteins, antibodies, nucleic acids, modified proteins, and
cells containing
cancer sequences are used in diagnostic assays. This can be performed on an
individual gene or
corresponding polypeptide level. In a preferred embodiment, the expression
profiles are used,
preferably in conjunction with high throughput screening techniques to allow
monitoring for
expression profile genes and/or corresponding polypeptides.
As described and defined herein, cancer proteins, including intracellular,
transmembrane, or secreted proteins, find use as markers of cancer, e.g., for
prognostic or
~0 diagnostic purposes. Detection of these proteins in putative cancer tissue
allows for detection,
prognosis, or diagnosis of cancer or similar disease, and for selection of
therapeutic strategy. In
one embodiment, antibodies are used to detect cancer proteins. A preferred
method separates
proteins from a sample by electrophoresis on a gel (typically a denaturing and
reducing protein
gel, but may be another type of gel, including isoelectric focusing gels and
the like). Following
separation of proteins, the cancer protein is detected, e.g., by
immunoblotting with antibodies
raised against the cancer protein.
In another preferred method, antibodies to the cancer protein find use in in
situ imaging
techniques, e.g., in histology. See, e.g., Asai, et al. (eds. 1993) Methods in
Cell Biology:
Antibodies in Cell Biology (vol. 37) Academic Press. In this method, cells are
contacted with
from one to many antibodies to the cancer protein(s). Following washing to
remove non-
specific antibody binding, the presence of the antibody or antibodies is
detected. In one
embodiment the antibody is detected by incubating with a secondary antibody
that contains a
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detectable label. In another method the primary antibody to the cancer
proteins) contains a
detectable label, e.g., an enzyme marker that can act on a substrate. In
another preferred
embodiment each one of multiple primary antibodies contains a distinct and
detectable label.
This method finds particular use in simultaneous screening for a plurality of
cancer proteins.
Many other histological imaging techniques are also provided by the invention.
In a preferred embodiment the label is detected in a fluorometer which has the
ability to
detect and distinguish emissions of different wavelengths. In addition, a
fluorescence activated
cell sorter (FACS) can be used in the method.
In another preferred embodiment, antibodies find use in diagnosing cancer from
blood,
serum, plasma, stool, and other samples. Such samples, therefore, are useful
as samples to be
probed or tested for the presence of cancer proteins. Antibodies can be used
to detect a cancer
protein by previously described immunoassay techniques including ELISA,
immunoblotting
(western blotting), immunoprecipitation, BIACORE technology and the like.
Conversely, the
presence of antibodies may indicate an immune response against an endogenous
cancer protein.
In a preferred embodiment, in situ hybridization of labeled cancer nucleic
acid probes to
tissue arrays is done. For example, arrays of tissue samples, including cancer
tissue and/or
normal tissue, are made. In situ hybridization (see, e.g., Ausubel, supra) is
then performed.
When comparing the fingerprints between an individual and a standard, a
diagnosis, a
prognosis, or a prediction may be based on the findings. It is further
understood that the genes
which indicate the diagnosis may differ from those which indicate the
prognosis and molecular
profiling of the condition of the cells may lead to distinctions
betweemresponsive or refractory
conditions or may be predictive of outcomes.
In a preferred embodiment, the cancer proteins, antibodies, nucleic acids,
modified
proteins, and cells containing cancer sequences are used in prognosis assays.
As above, gene
expression profiles can be generated that correlate to cancer, clinical,
pathological, or other
information, in terms of long term prognosis. Again, this may be done on
either a protein or
gene level, with the use of genes being preferred. Single or multiple genes
may be useful in
various combinations. As above, cancer probes may be attached to biochips for
the detection
and quantification of cancer sequences in a tissue or patient. The assays
proceed as outlined
above for diagnosis. PCR method may provide more sensitive and accurate
quantification.


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Assays for therapeutic compounds
In a preferred embodiment, the proteins, nucleic acids, and antibodies as
described
herein are used in drug screening assays. The cancer proteins, antibodies,
nucleic acids,
modified proteins, and cells containing cancer sequences are used in drug
screening assays or
by evaluating the effect of drug candidates on a "gene expression profile" or
expression profile
of polypeptides. In a preferred embodiment, the expression profiles are used,
preferably in
conjunction with high throughput screening techniques, to allow monitoring for
expression
profile genes after treatment with a candidate agent (e.g., Zlokarnik, et al.
(1998) Science
279:84-88; Heid (1996) Genome Res. 6:986-994.
In a preferred embodiment, the cancer proteins, antibodies, nucleic acids,
modified
proteins and cells containing the native or modified cancer proteins are used
in screening
assays. That is, the present invention provides novel methods for screening
for compositions
which modulate the cancer phenotype or an identified physiological function of
a cancer
protein. As above, this can be done on an individual gene level or by
evaluating the effect of
drug candidates on a "gene expression profile". In a preferred embodiment, the
expression
profiles are used, preferably in conjunction with high throughput screening
techniques, to allow
monitoring for expression profile genes after treatment with a candidate
agent, see Zlokarnik,
supra.
Having identified the differentially expressed genes herein, a variety of
assays may be
performed. In a preferred embodiment, assays may be run on an individual gene
or protein
level. That~is, having identified a particular gene as up regulated in cancer,
test compounds can
be screened for the ability to modulate gene expression or for binding to the
cancer protein.
"Modulation" thus includes both an increase and a decrease in gene expression.
The preferred
amount of modulation will depend on the original change of the gene expression
in normal
versus tissue undergoing cancer, with changes of at least 10%, preferably 50%,
more preferably
100-300%, and in some embodiments 300-1000% or greater. Thus, if a gene
exhibits a 4-fold
increase in cancer tissue compared to normal tissue, a decrease of about four-
fold is often
desired; similarly, a 10-fold decrease in cancer tissue compared to normal
tissue often provides
a target value of a 10-fold increase in expression to be induced by the test
compound.
The amount of gene expression may be monitored using nucleic acid probes and
the
quantification of gene expression levels, or, alternatively, the gene product
itself can be
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monitored, e.g., through the use of antibodies to the cancer protein and
standard immunoassays.
Proteomics and separation techniques may also allow quantification of
expression.
In a preferred embodiment, gene expression or protein monitoring of a number
of
entities, e.g., an expression profile, is monitored simultaneously. Such
profiles will typically
involve a plurality of those entities described herein.
In this embodiment, the cancer nucleic acid probes are attached to biochips as
outlined
herein for the detection and quantification of cancer sequences in a
particular cell.
Alternatively, PCR may be used. Thus, a series, e.g., of microtiter plate, may
be used with
dispensed primers in desired wells. A PCR reaction can then be performed and
analyzed for
each well.
Modulators of cancer
Expression monitoring can be performed to identify compounds that modify the
expression of one or more cancer-associated sequences, e.g., a polynucleotide
sequence set out
in the tables. Generally, in a preferred embodiment, a test modulator is added
to the cells prior
to analysis. Moreover, screens are also provided to identify agents that
modulate cancer,
modulate cancer proteins, bind to a cancer protein, or interfere with the
binding of a cancer
protein and an antibody or other binding partner.
The term "test compound" or "drug candidate" or "modulator" or grammatical
equivalents as used herein describes a molecule, e.g., protein, oligopeptide,
small organic
molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity
to directly or
indirectly alter the cancer phenotype or the expression of a cancer sequence,
e.g., a nucleic acid
or protein sequence. In preferred embodiments, modulators alter expression
profiles, or
expression profile nucleic acids or proteins provided herein. In one
embodiment, the modulator
suppresses a cancer phenotype, e.g., to a normal or non-malignant tissue
fingerprint. In another
embodiment, a modulator induced a cancer phenotype. Generally, a plurality of
assay mixtures
are run in parallel with different agent concentrations to obtain a
differential response to the
various concentrations. Typically, one of these concentrations serves as a
negative control, e.g.,
at zero concentration or below the level of detection.
Drug candidates encompass numerous chemical classes, though typically they are
organic molecules, preferably small organic compounds having a molecular
weight of more
than 100 and less than about 2,500 daltons. Preferred small molecules are less
than 2000, or
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less than 1500, or less than 1000, or less than 500 D. Candidate agents
comprise functional
groups necessary for structural interaction with proteins, particularly
hydrogen bonding, and
typically include at least an amine, carbonyl, hydroxyl or carboxyl group,
preferably at least two
of the functional chemical groups. The candidate agents often comprise
cyclical carbon or
heterocyclic structures and/or aromatic or polyaromatic structures substituted
with one or more
of the above functional groups. Candidate agents are also found among
biomolecules including
peptides, saccha.rides, fatty acids, steroids, purines, pyrimidines,
derivatives, structural analogs,
or combinations thereof. Particularly preferred are peptides.
In one aspect, a modulator will neutralize the effect of a cancer protein. By
"neutralize"
is meant that activity of a protein is inhibited or blocked and the consequent
effect on the cell.
In certain embodiments, combinatorial libraries of potential modulators will
be screened
for an ability to bind to a cancer polypeptide or to modulate activity.
Conventionally, new
chemical entities with useful properties are generated by identifying a
chemical compound
(called a "lead compound") with some desirable property or activity, e.g.,
inhibiting activity,
creating variants of the lead compound, and evaluating the property and
activity of those variant
compounds. Often, high throughput screening (HTS) methods are employed for
such an
analysis. See, e.g., Janzen (2002) High Throughput Screening: Methods and
Protocols
Humana; Devlin (ed. 1997) High Throughput Screening: The Discovery of
Bioactive
Substances Dekker; and Mei and Czarnik (eds. 2002) Integrated Drug Discovery
Techniques
Dekker.
In one preferred embodiment, high throughput screening methods involve
providing a
library containing a large number of potential therapeutic compounds
(candidate compounds).
Such "combinatorial chemical libraries" axe then screened in one or more
assays to identify
those library members (particular chemical species or subclasses) that display
a desired
characteristic activity. The compounds thus identified can serve as
conventional "lead
compounds" or can themselves be used as potential or actual therapeutics.
A combinatorial chemical library is a collection of diverse chemical compounds
generated by either chemical synthesis or biological synthesis by combining a
number of
chemical "building blocks" such as reagents. For example, a linear
combinatorial chemical
library, such as a polypeptide (e.g., mutein) library, is formed by combining
a set of chemical
building blocks called amino acids in every possible way for a given compound
length (e.g., the
number of amino acids in a polypeptide compound). Millions of chemical
compounds can be
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CA 02459219 2004-03-17
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synthesized through such combinatorial mixing of chemical building blocks
(Gallop, et al.
(1994) J. Med. Chem. 37:1233-1251).
Preparation and screening of combinatorial chemical libraries is well known.
Such
combinatorial chemical libraries include, but are not limited to, peptide
libraries (see, e.g., U.S.
Patent No. 5,010,175, Furka (1991) Pelt. Prot. Res. 37:487-493, Houghton, et
al. (1991) Nature
354:84-88), peptoids (PCT Publication No WO 91/19735), encoded peptides (PCT
Publication
WO 93/20242), random bio-oligomers (PCT Publication WO 92/00091),
benzodiazepines (U.5.
Pat. No. 5,288,514), diversomers such as hydantoins, benzodiazepines and
dipeptides (Hobbs, et
al. (1993) Proc. Nat. Acad. Sci. USA 90:6909-6913, vinylogous polypeptides
(Hagihara, et al.
(1992) J. Amer. Chem. Soc. 114:6568-570), nonpeptidal peptidomimetics with a
Beta-D-
Glucose scaffolding (Hirschmann, et al. (1992) J. Amer. Chem. Soc. 114:9217-
9218),
analogous organic syntheses of small compound libraries (Chen, et al. (1994)
J. Amer. Chem.
Soc. 116:2661-662), oligocarbamates (Cho, et al. (1993) Science 261:1303-
1305), and/or
peptidyl phosphonates (Campbell, et al. (1994) J. Org. Chem. 59:658-xxx). See,
generally,
Gordon, et al. (1994) J. Med. Chem. 37:1385-1401, nucleic acid libraries (see,
e.g., Stratagene,
Corp.), peptide nucleic acid libraries (see, e.g., U.S. Patent 5,539,083),
antibody libraries (see,
e.g., Vaughn, et al. (1996) Nature Biotechnolo~y 14(3):309-314, and
PCTlLJS96/10287),
carbohydrate libraries (see, e.g., Liang, et al. (1996) Science 274:1520-1522,
and U.S. Patent
No. 5,593,853), and small organic molecule libraries (see, e.g.,
benzodiazepines, page 33 Baum
(Jan 18, 1993) C&EN; isoprenoids, U.S. Patent No. 5,569,588; thiazolidinones
and
metathiazanones, U.S. Patent No. 5,549,974; pyrrolidines, U.S. Patent Nos.
5,525,735 and
5,519,134; morpholino compounds, U.S. Patent No. 5,506,337; benzodiazepines,
U.S. Patent
No. 5,288,514; and the like).
Devices for the preparation of combinatorial libraries are commercially
available (see,
e.g., 357 MPS, 390 MPS, Advanced Chem Tech, Louisville KY, Symphony, Rainin,
Woburn,
MA, 433A Applied Biosystems, Foster City, CA, 9050 Plus, Millipore, Bedford,
MA).
A number of well known robotic systems have also been developed for solution
phase
chemistries. These systems include automated workstations like the automated
synthesis
apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and
many robotic
systems utilizing robotic arms (Zymate II, Zymark Corporation, Hopkinton,
Mass.; Orca,
Hewlett-Packard, Palo Alto, Calif.), which mimic the manual synthetic
operations performed by
a chemist. The above devices are suitable for use with the present invention.
The nature and
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implementation of modifications to these devices (if any) so that they can
operate as discussed
herein will be apparent. In addition, numerous combinatorial libraries are
themselves
commercially available (see, e.g., ComGenex, Princeton, N.J., Asinex, Moscow,
Ru, Tripos,
Inc., St. Louis, MO, ChemStar, Ltd, Moscow, RU, 3D Pharmaceuticals, Exton, PA,
Martek
Biosciences, Columbia, MD, etc.).
The assays to identify modulators are amenable to high throughput screening.
Preferred
assays thus detect enhancement or inhibition of cancer gene transcription,
inhibition, or
enhancement of polypeptide expression, and inhibition or enhancement of
polypeptide activity.
High throughput assays for the presence, absence, quantification, or other
properties of
particular nucleic acids or protein products are well known. Similarly,
binding assays and
reporter gene assays are similarly well known. Thus, e.g., U.S. Patent No.
5,559,410 discloses
high throughput screening methods for proteins, U.S. Patent No. 5,55,639
discloses high
throughput screening methods for nucleic acid binding (e.g., in arrays), while
U.S. Patent Nos.
5,576,220 and 5,541,061 disclose high throughput methods of screening for
ligand/antibody
binding.
In addition, high throughput screening systems are commercially available
(see, e.g.,
Zymark Corp., Hopkinton, MA; Air Technical Industries, Mentor, OH; Beckman
Instruments,
Inc. Fullerton, CA; Precision Systems, Inc., Natick, MA, etc.). These systems
typically
automate entire procedures, including sample and reagent pipetting, liquid
dispensing, timed
incubations, and final readings of the microplate in detectors) appropriate
for the assay. These
configurable systems provide high throughput and rapid start up as well as a
high degre~of
flexibility and customization. The manufacturers of such systems provide
detailed protocols for
various high throughput systems. Thus, e.g., Zymark Corp. provides technical
bulletins
describing screening systems for detecting the modulation of gene
transcription, ligand binding,
and the like.
In one embodiment, modulators are proteins, often naturally occurring proteins
or
fragments of naturally occurring proteins. Thus, e.g., cellular extracts
containing proteins, or
random or directed digests of proteinaceous cellular extracts, may be used. In
this way libraries
of proteins may be made for screening in the methods of the invention.
Particularly preferred in
this embodiment are libraries of bacterial, fungal, viral, and mammalian
proteins, with the latter
being preferred, and human proteins being especially preferred. Particularly
useful test


CA 02459219 2004-03-17
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compound will be directed to the class of proteins to which the target
belongs, e.g., substrates
for enzymes or ligands and receptors.
In a preferred embodiment, modulators are peptides of from about 5-30 amino
acids,
with from about 5-20 amino acids being preferred, and from about 7-15 being
particularly
preferred. The peptides may be digests of naturally occurnng proteins, random
peptides, or
"biased" random peptides. By "randomized" or grammatical equivalents herein is
meant that
each nucleic acid and peptide consists of essentially random nucleotides and
amino acids,
respectively. Since generally these random peptides (or nucleic acids,
discussed below) are
chemically synthesized, they may incorporate a nucleotide or amino acid at any
position. The
synthetic process can be designed to generate randomized proteins or nucleic
acids, to allow the
formation of all or most of the possible combinations over the length of the
sequence, thus
forming a library of randomized candidate bioactive proteinaceous agents.
In one embodiment, the library is fully randomized, with no sequence
preferences or
constants at any position. In a preferred embodiment, the library is biased.
That is, some
positions within the sequence are either held constant, or are selected from a
limited number of
possibilities. For example, in a preferred embodiment, the nucleotides or
amino acid residues
are randomized within a defined class, e.g., of hydrophobic amino acids,
hydrophilic residues,
sterically biased (either small or large) residues, towards the creation of
nucleic acid binding
domains, the creation of cysteines, for cross-linking, prolines for SH-3
domains, serines,
threonines, tyrosines, or histidines for phosphorylation sites, etc., or to
purines, etc.
Modulators of cancer can also be nucleic acids, as defined above.
As described above generally for proteins, nucleic acid modulating agents may
be
naturally occurring nucleic acids, random nucleic acids, or "biased" random
nucleic acids. For
example, digests of prokaryotic or eukaryotic genomes may be used as is
outlined above for
proteins.
In a preferred embodiment, the candidate compounds are organic chemical
moieties, a
wide variety of which are available in the literature.
After the candidate agent has been added and the cells allowed to incubate for
some
period of time, the sample containing a target sequence to be analyzed is
added to the biochip.
If required, the target sequence is prepared using known techniques. For
example, the sample
may be treated to lyse the cells, using known lysis buffers, electroporation,
etc., with
purification and/or amplification such as PCR performed as appropriate. For
example, an in
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vitro transcription with labels covalently attached to the nucleotides is
performed. Generally,
the nucleic acids are labeled with biotin-FITC or PE, or with cy3 or cy5.
In a preferred embodiment, the target sequence is labeled with, e.g., a
fluorescent, a
chemiluminescent, a chemical, or a radioactive signal, to provide a means of
detecting the target
sequence's specific binding to a probe. The label also can be an enzyme, such
as, alkaline
phosphatase or horseradish peroxidase, which when provided with an appropriate
substrate
produces a product that can be detected. Alternatively, the label can be a
labeled compound or
small molecule, such as an enzyme inhibitor, that binds but is not catalyzed
or altered by the
enzyme. The label also can be a moiety or compound, such as, an epitope tag or
biotin which
specifically binds to streptavidin. For the example of biotin, the
streptavidin is labeled as
described above, thereby, providing a detectable signal for the bound target
sequence. Unbound
labeled streptavidin is typically removed prior to analysis.
These assays can be direct hybridization assays or can comprise "sandwich
assays",
which include the use of multiple probes, as is generally outlined in U.S.
Patent Nos. 5,681,702,
5,597,909, 5,545,730, 5,594,117, 5,591,584, 5,571,670, 5,580,731, 5,571,670,
5,591,584,
5,624,802, 5,635,352, x,594,118, 5,359,100, 5,124,246, and 5,681,697, all of
which are hereby
incorporated by reference. In this embodiment, in general, the target nucleic
acid is prepared as
outlined above, and then added to the biochip comprising a plurality of
nucleic acid probes,
under conditions that allow the formation of a hybridization complex.
A variety of hybridization conditions may be used in the present invention,
including
high, moderate, and low stringency conditions as outlined above. The assays
are generally run
under stringency conditions which allows formation of the label probe
hybridization complex
only in the presence of target. Stringency can be controlled by altering a
step parameter that is a
thermodynamic variable, including, but not limited to, temperature, formamide
concentration,
salt concentration, chaotropic salt concentration, pH, organic solvent
concentration, etc.
These parameters may also be used to control non-specific binding, as is
generally
outlined in U.S. Patent No. 5,681,697. Thus it may be desirable to perform
certain steps at
higher stringency conditions to reduce non-specific binding.
The reactions outlined herein may be accomplished in a variety of ways.
Components
of the reaction may be added simultaneously, or sequentially, in different
orders, with preferred
embodiments outlined below. In addition, the reaction may include a variety of
other reagents.
These include salts, buffers, neutral proteins, e.g., albumin, detergents,
etc. which may be used
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to facilitate optimal hybridization and detection, andlor reduce non-specific
or background
interactions. Reagents that otherwise improve the efficiency of the assay,
such as protease
inhibitors, nuclease inhibitors, anti-microbial agents, etc., may also be used
as appropriate,
depending on the sample preparation methods and purity of the target.
The assay data are analyzed to determine the expression levels, and changes in
expression levels as between states of individual genes, forming a gene
expression profile.
Screens are performed to identify modulators of the cancer phenotype. In one
embodiment, screening is performed to identify modulators that can induce or
suppress a
particular expression profile, thus preferably generating the associated
phenotype. In another
embodiment, e.g., for diagnostic applications, having identified
differentially expressed genes
important in a particular state, screens can be performed to identify
modulators that alter
expression of individual genes. In an another embodiment, screening is
performed to identify
modulators that alter a biological function of the expression product of a
differentially
expressed gene. Again, having identified the importance of a gene in a
particular state, screens
are performed to identify agents that bind and/or modulate the biological
activity of the gene
product.
In addition, screens can be done for genes that are induced in response to a
candidate
agent or treatment process. After identifying a modulator based upon its
ability to suppress a
cancer expression pattern leading to a normal expression pattern (or its
converse), or to
modulate a single cancer gene expression profile so as to mimic the expression
of the gene from
normal tissue, a screen as described above can be performed to identify genes
that are
specifically modulated in response to the agent. Comparing expression profiles
between normal
tissue and agent treated cancer tissue reveals genes that are not expressed in
normal tissue or
cancer tissue, but are expressed in agent treated tissue. These agent-specific
sequences can be
identified and used by methods described herein for cancer genes or proteins.
In particular,
these sequences and the proteins they encode fmd use in marking or identifying
agent treated
cells. In addition, antibodies can be raised against the agent induced
proteins and used to target
novel therapeutics to the treated cancer tissue sample.
Thus, in one embodiment, a test compound is administered to a population of
cancer
cells that have an associated cancer expression profile. By "administration"
or "contacting"
herein is meant that the candidate agent is added to the cells in such a
manner as to allow the
agent to act upon the cell, whether by uptake and intracellular action, or by
action at the cell
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surface. In some embodiments, nucleic acid encoding a proteinaceous candidate
agent (e.g., a
peptide) may be put into a viral construct such as an adenoviral or retroviral
construct, and
added to the cell, such that expression of the peptide agent is accomplished,
e.g., PCT
LTS97/01019. Regulatable gene therapy systems can also be used.
Once a test compound has been administered to the cells, the cells can be
washed if
desired and are allowed to incubate under preferably physiological conditions
for some period
of time. The cells are then harvested and a new gene expression profile is
generated, as outlined
herein.
Thus, e.g., cancer or non-malignant tissue may be screened for agents that
modulate,
e.g., induce or suppress a cancer phenotype. A change in at least one gene,
preferably many, of
the expression profile indicates that the agent has an effect on cancer
activity. By defining such
a signature for the cancer phenotype, screens for new drugs that alter
the~phenotype can be
devised. With this approach, the drug target need not be known and need not be
represented in
the original expression screening platform, nor does the level of transcript
for the target protein
need to change.
In a preferred embodiment, as outlined above, screens may be done on
individual genes
and gene products (proteins). That is, having identified a particular
differentially expressed
gene as important in a particular state, screening of modulators of either the
expression of the '
gene or the gene product itself can be done. The gene products of
differentially expressed genes
are sometimes referred to herein as "cancer proteins" or a "cancer modulatory
protein". The
cancer modulatory protein may be a fragment, or alternatively, be the full
length protein to the
fragment encoded by the nucleic acids of the Tables. Preferably, the cancer
modulatory protein
is a fragment. In a preferred embodiment, the cancer amino acid sequence which
is used to
determine sequence identity or similarity is encoded by a nucleic acid of the
Tables. In another
embodiment, the sequences are naturally occurring allelic variants of a
protein encoded by a
nucleic acid of the Tables. In another embodiment, the sequences are sequence
variants as
further described herein.
Preferably, the cancer modulatory protein is a fragment of about 14-24 amino
acids
long. More preferably the fragment is a soluble fragment. Preferably, the
fragment includes a
non-transmembrane region. In a preferred embodiment, the fragment has an N-
terminal Cys to
aid in solubility. In one embodiment, the C-terminus of the fragment is kept
as a free acid and
the N-terminus is a free amine to aid in coupling, e.g., to cysteine.
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In one embodiment the cancer proteins are conjugated to an immunogenic agent
as
discussed herein. In one embodiment the cancer protein is conjugated to BSA.
Measurements of cancer polypeptide activity, or of cancer or the cancer
phenotype can
be performed using a variety of assays. For example, the effects of the test
compounds upon the
function of the cancer polypeptides can be measured by examining parameters
described above.
A suitable physiological change that affects activity can be used to assess
the influence of a test
compound on the polypeptides of this invention. When the functional
consequences are
determined using intact cells or animals, one can also measure a variety of
effects such as, in the
case of cancer associated with tumors, tumor growth, tumor metastasis,
neovascularization,
hormone release, transcriptional changes to both known and uncharacterized
genetic markers
(e.g., northern blots), changes in cell metabolism such as cell growth or pH
changes, and
changes in intracellular second messengers such as cGMP. In the assays of the
invention,
mammalian cancer polypeptide is typically used, e.g., mouse, preferably human.
Assays to identify compounds with modulating activity can be performed in
vitro. For
example, a cancer polypeptide is first contacted with a potential modulator
and incubated for a
suitable amount of time, e.g., from 0.5-48 hours. In one embodiment, the
cancer polypeptide
levels are determined in vitro by measuring the level of protein or mRNA. The
level of protein
is typically measured using immunoassays such as western blotting, ELISA, and
the like with
an antibody that selectively binds to the cancer polypeptide or a fragment
thereof. For
measurement of mRNA, amplification, e.g., using PCR, LCR, or hybridization
assays, e.g.,
northern hybridization, RNAse protection, dot blotting, are preferred. The
level of protein or
mRNA is typically detected using directly or indirectly labeled detection
agents, e.g.,
fluorescently or radioactively labeled nucleic acids, radioactively or
enzymatically labeled
antibodies, and the like, as described herein.
Alternatively, a reporter gene system can be devised using a cancer protein
promoter
operably linked to a reporter gene such as luciferase, green fluorescent
protein, CAT, or ~3-gal.
The reporter construct is typically transfected into a cell. After treatment
with a potential
modulator, the amount of reporter gene transcription, translation, or activity
is measured
according to standard techniques.
In a preferred embodiment, as outlined above, screens may be done on
individual genes
and gene products (proteins). That is, having identified a particular
differentially expressed
gene as important in a particular state, screening of modulators of the
expression of the gene or


CA 02459219 2004-03-17
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the gene product itself can be done. The gene products of differentially
expressed genes are
sometimes referred to herein as "cancer proteins." The cancer protein may be a
fragment, or
alternatively, the full length protein to a fragment shown herein.
In one embodiment, screening for modulators of expression of specific genes is
performed. Typically, the expression of only one or a few genes are evaluated.
In another
embodiment, screens are designed to first find compounds that bind to
differentially expressed
proteins. These compounds are then evaluated for the ability to modulate
differentially
expressed activity. Moreover, once initial candidate compounds are identified,
variants can be
further screened to better evaluate structure activity relationships.
In a preferred embodiment, binding assays are done. In general, purified or
isolated
gene product is used; that is, the gene products of one or more differentially
expressed nucleic
acids are made. For example, antibodies are generated to the protein gene
products, and
standard immunoassays are run to determine the amount of protein present.
Alternatively, cells
comprising the cancer proteins can be used in the assays.
Thus, in a preferred embodiment, the methods comprise combining a cancer
protein and
a candidate compound, and determining the binding of the compound to the
cancer protein.
Preferred embodiments utilize the human cancer protein, although other
mammalian proteins
may also be used, e.g., for the development of animal models of human disease.
In some
embodiments, as outlined herein, variant or derivative cancer proteins may be
used.
Generally, in a preferred embodiment of the methods herein, the cancer protein
or the
candidate agent is non-diffusably bound to an insoluble support, preferably
having isolated
sample receiving areas (e.g., a microtiter plate, an array, etc.). The
insoluble supports may be
made of a composition to which the compositions can be bound, is readily
separated from
soluble material, and is otherwise compatible with the overall method of
screening. The surface
of such supports may be solid or porous and of a convenient shape. Examples of
suitable
insoluble supports include microtiter plates, arrays, membranes, and beads.
These are typically
made of glass, plastic (e.g., polystyrene), polysaccharides, nylon or
nitrocellulose, teflonTM, etc.
Microtiter plates and arrays are especially convenient because a large number
of assays can be
carned out simultaneously, using small amounts of reagents and samples. The
particular
manner of binding of the composition is typically not crucial so long as it is
compatible with the
reagents and overall methods of the invention, maintains the activity of the
composition, and is
nondiffusable. Preferred methods of binding include the use of antibodies
(which do not
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sterically block either the ligand binding site or activation sequence when
the protein is bound
to the support), direct binding to "sticky" or ionic supports, chemical
crosslinking, the synthesis
of the protein or agent on the surface, etc. Following binding of the protein
or agent, excess
unbound material is removed by washing. The sample receiving areas may then be
blocked
through incubation with bovine serum albumin (BSA), casein, or other innocuous
protein or
other moiety.
In a preferred embodiment, the cancer protein is bound to the support, and a
test
compound is added to the assay. Alternatively, the candidate agent is bound to
the support and
the cancer protein is added. Novel binding agents include specific antibodies,
non-natural
binding agents identified in screens of chemical libraries, peptide analogs,
etc. Of particular
interest are screening assays for agents that have a low toxicity for human
cells. A wide variety
of assays may be used for this purpose, including labeled in vitro protein-
protein binding assays,
electrophoretic mobility shift assays, immunoassays for protein binding,
functional assays
(phosphorylation assays, etc.), and the like.
The determination of the binding of the test modulating compound to the cancer
protein
may be done in a number of ways. In a preferred embodiment, the compound is
labeled, and
binding determined directly, e.g., by attaching all or a portion of the cancer
protein to a solid
support, adding a labeled candidate agent (e.g., a fluorescent label), washing
off excess reagent,
and determining whether the label is present on the solid support. Various
blocking and
washing steps may be utilized as appropriate.
In some embodiments, only one of the components is labeled, e.g., the proteins
(or
proteinaceous candidate compounds) can be labeled. Alternatively, more than
one component
can be labeled with different labels, e.g., 125I for the proteins and a
fluorophor for the
compound. Proximity reagents, e.g., quenching or energy transfer reagents are
also useful.
In one embodiment, the binding of the test compound is determined by
competitive
binding assay. The competitor may be a binding moiety known to bind to the
target molecule
(e.g., a cancer protein), such as an antibody, peptide, binding partner,
ligand, etc. TJnder certain
circumstances, there may be competitive binding between the compound and the
binding
moiety, with the binding moiety displacing the compound. In one embodiment,
the test
compound is labeled. Either the compound, or the competitor, or both, is added
first to the
protein for a time sufficient to allow binding, if present. Incubations may be
performed at a
temperature which facilitates optimal activity, typically between about 4-
40° C. Incubation
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periods are typically optimized, e.g., to facilitate rapid high throughput
screening. Typically
between 0.1-1 hour will be sufficient. Excess reagent is generally removed or
washed away.
The second component is then added, and the presence or absence of the labeled
component is
followed, to indicate binding.
In a preferred embodiment, the competitor is added first, followed by a test
compound.
Displacement of the competitor is an indication that the test compound is
binding to the cancer
protein and thus is capable of binding to, and potentially modulating, the
activity of the cancer
protein. In this embodiment, either component can be labeled. Thus, e.g., if
the competitor is
labeled, the presence of label in the wash solution indicates displacement by
the agent.
Alternatively, if the test compound is labeled, the presence of the label on
the support indicates
displacement.
In an alternative embodiment, the test compound is added first, with
incubation and
washing, followed by the competitor. The absence of binding by the competitor
may indicate
that the test compound is bound to the cancer protein with a higher affinity.
Thus, if the test
compound is labeled, the presence of the label on the support, coupled with a
lack of competitor
binding, may indicate that the test compound is capable of binding to the
cancer protein.
In a preferred embodiment, the methods comprise differential screening to
identity
agents that are capable of modulating the activity of the cancer proteins. In
one embodiment,
the methods comprise combining a cancer protein and a competitor in a first
sample. A second
sample comprises a test compound, a cancer protein, and a competitor. The
binding of the
competitor is determined for both samples, and a change, or difference in
binding between the
two samples indicates the presence of an agent capable of binding to the
cancer protein and
potentially modulating its activity. That is, if the binding of the competitor
is different in the
second sample relative to the first sample, the agent is capable of binding to
the cancer protein.
Alternatively, differential screening is used to identify drug candidates that
bind to the
native cancer protein, but cannot bind to modified cancer proteins. The
structure of the cancer
protein may be modeled, and used in rational drug design to synthesize agents
that interact with
that site. Drug candidates that affect the activity of a cancer protein are
also identified by
screening drugs for the ability to either enhance or reduce the activity of
the protein.
Positive controls and negative controls may be used in the assays. Preferably
control
and test samples are performed in at least triplicate to obtain statistically
significant results.
Incubation of all samples is for a time sufficient for the binding of the
agent to the protein.
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Following incubation, samples are washed free of non-specifically bound
material and the
amount of bound, generally labeled agent determined. For example, where a
radiolabel is
employed, the samples may be counted in a scintillation counter to determine
the amount of
bound compound.
A variety of other reagents may be included in the screening assays. These
include
reagents like salts, neutral proteins, e.g., albumin, detergents, etc., which
may be used to
facilitate optimal protein-protein binding andlor reduce non-specific or
background interactions.
Also reagents that otherwise improve the efficiency of the assay, such as
protease inhibitors,
nuclease inhibitors, anti-microbial agents, etc., may be used. The mixture of
components may
be added in an order that provides for the requisite binding.
In a preferred embodiment, the invention provides methods for screening for a
compound capable of modulating the activity of a cancer protein. The methods
comprise
adding a test compound, as defined above, to a cell comprising cancer
proteins. Preferred cell
types include almost any cell. The cells contain a recombinant nucleic acid
that encodes a
cancer protein. In a preferred embodiment, a library of candidate agents are
tested on a plurality
of cells.
In one aspect, the assays are evaluated in the presence or absence or previous
or
subsequent exposure of physiological signals, e.g., hormones, antibodies,
peptides, antigens,
cytokines, growth factors, action potentials, pharmacological agents including
chemotherapeutics, radiation, carcinogenics, or other cells (e.g., cell-cell
contacts). In another
example, the determinations are determined at different stages of the cell
cycle process.
In this way, compounds that modulate cancer agents are identified. Compounds
with
pharmacological activity are able to enhance or interfere with the activity of
the cancer protein.
Once identified, similar structures are evaluated to identify critical
structural feature of the
compound.
In one embodiment, a method of inhibiting cancer cell division is provided.
The method
comprises administration of a cancer inhibitor. In another embodiment, a
method of inhibiting
cancer is provided. The method may comprise administration of a cancer
inhibitor. In a further
embodiment, methods of treating cells or individuals with cancer are provided,
e.g., comprising
administration of a cancer inhibitor.
In one embodiment, a cancer inhibitor is an antibody as discussed above. In
another
embodiment, the cancer inhibitor is an antisense molecule.
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A variety of cell growth, proliferation, viability, and metastasis assays are
available, as
described below.
Soft agar growth or colony formation in suspension
Normal cells require a solid substrate to attach and grow. When the cells are
transformed, they lose this phenotype and grow detached from the substrate.
For example,
transformed cells can grow in stirred suspension culture or suspended in semi-
solid media, such
as semi-solid or soft agar. The transformed cells, when transfected with tumor
suppressor
genes, regenerate normal phenotype and require a solid substrate to attach and
grow. Soft agar
growth or colony formation in suspension assays can be used to identify
modulators of cancer
sequences, which when expressed in host cells, inhibit abnormal cellular
proliferation and
transformation. A therapeutic compound would reduce or eliminate the host
cells' ability to
grow in stirred suspension culture or suspended in semi-solid media, such as
semi-solid or soft.
Techniques for soft agar growth or colony formation in suspension assays are
described,
e.g., in Freshney (1998) Culture of Animal Cells: A Manual of Basic Technique
(3d ed.) Wiley-
Liss; Freshney (2000) Culture of Animal Cells: A Manual of Basic Technique
(4th ed.) Wiley-
Liss; and Garkavtsev, et al. (1996) Nature Genet. 14:415-20.
Contact inhibition and density limitation of growth
Normal cells typically grow in a flat and organized pattern in a petri dish
until they
touch other cells. When the cells touch one another, they are contact
inhibited and stop
growing. When cells are transformed, however, the cells are not contact
inhibited and continue
to grow to high densities in disorganized foci. Thus, the transformed cells
grow to a higher
saturation density than normal cells. This can be detected morphologically by
the formation of
a disoriented monolayer of cells or rounded cells in foci within the regular
pattern of normal
surrounding cells. Alternatively, labeling index with (3H)-thymidine at
saturation density can
be used to measure density limitation of growth. See Freshney (2000), supra.
The transformed
cells, when transfected with tumor suppressor genes, regenerate a normal
phenotype and
become contact inhibited and would grow to a lower density.
In this assay, labeling index with (3H)-thymidine at saturation density is a
preferred
method of measuring density limitation of growth. Transformed host cells are
transfected with
a cancer-associated sequence and are grown for 24 hours at saturation density
in non-limiting
medium conditions. The percentage of cells labeling with (3H)-thymidine is
determined
autoradiographically. See, Freshney (1998), supra.


CA 02459219 2004-03-17
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Growth factor or serum dependence
Transformed cells typically have a lower serum dependence than their normal
counterparts (see, e.g., Temin (1966) J. Natl. Cancer Insti. 37:167-175;
Eagle, et a1.(1970) J.
Exp. Med. 131:836-879); Freshney, supra. This is in part due to release of
various growth
factors by the transformed cells. Growth factor or serum dependence of
transformed host cells
can be compared with that of control.
Tumor specific markers levels
Tumor cells release an increased amount of certain factors (hereinafter "tumor
specific
markers") than their normal counterparts. For example, plasminogen activator
(PA) is released
from human glioma at a higher level than from normal brain cells (see, e.g.,
Gullino
"Angiogenesis, tumor vascularization, and potential interference with tumor
growth" pp. 178-
184 in Mihich (ed. 1985) Biolo ,ical Responses in Cancer Plenum. Similarly,
tumor
angiogenesis factor (TAF) is released at a higher level in tumor cells than
their normal .
counterparts. See, e.g., Folkman (1992) Sem. Cancer Biol. 3:89-96.
Various techniques which measure the release of these factors are described in
Freshney
(1998), supra. Also, see, Unkeless, et al. (1974) J. Biol. Chem. 249:4295-
4305; Strickland and
Beers (1976) J. Biol. Chem. 251:5694-5702; Whur, et al. (1980) Br. J. Cancer
42:305-312;
Gullino "Angiogenesis, tumor vascularization, and potential interference with
tumor growth"
pp. 178-184 in Mihich (ed. 1985) Biological Responses in Cancer Plenum;
Freshney (1985)
Anticancer Res. 5:111-130.
Invasiveness into Matrigel
The degree of invasiveness into Matrigel or some other extracellular matrix
constituent
can be used as an assay to identify compounds that modulate cancer-associated
sequences.
Tumor cells exhibit a good correlation between malignancy and invasiveness of
cells into
Matrigel or some other extracellular matrix constituent. In this assay,
tumorigenic cells are
typically used as host cells. Expression of a tumor suppressor gene in these
host cells would
decrease invasiveness of the host cells.
Techniques described in Freshney (1994), supra, can be used. Briefly, the
level of
invasion of host cells can be measured by using filters coated with Matrigel
or some other
extracellular matrix constituent. Penetration into the gel, or through to the
distal side of the
filter, is rated as invasiveness, and rated histologically by number of cells
and distance moved,
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or by prelabeling the cells with 1251 and counting the radioactivity on the
distal side of the filter
or bottom of the dish. See, e.g., Freshney (1984), supra.
Tumor growth in vivo
Effects of cancer-associated sequences on cell growth can be tested in
transgenic or
immune-suppressed mice. Knock-out transgenic mice can be made, in which the
cancer gene is
disrupted or in which a cancer gene is inserted. Knock-out transgenic mice can
be made by
insertion of a marker gene or other heterologous gene into the endogenous
cancer gene site in
the mouse genome via homologous recombination. Such mice can also be made by
substituting
the endogenous cancer gene with a mutated version of the cancer gene, or by
mutating the
endogenous cancer gene, e.g., by exposure to carcinogens.
A DNA construct is introduced into the nuclei of embryonic stem cells. Cells
containing
the newly engineered genetic lesion are injected into a host mouse embryo,
which is re-
implanted into a recipient female. Some of these embryos develop into chimeric
mice that
possess germ cells partially derived from the mutant cell line. Therefore, by
breeding the
chimeric mice it is possible to obtain a new line of mice containing the
introduced genetic lesion
(see, e.g., Capecchi, et al. (1989) Science 244:1288-1292). Chimeric targeted
mice can be
derived according to Hogan, et al. (1988) Mani~ulatin~ the Mouse Embryo: A
Laboratory
Manual CSH Press; and Robertson (ed. 1987) Teratocarcinomas and Embryonic Stem
Cells: A
Practical Approach IRL Press, Washington, D.C.
Alternatively, various immune-suppressed or immune-deficient host animals can
be
used. For example, genetically athyrnic "nude" mouse (see, e.g., Giovanella,
et al. (1974) J.
Natl. Cancer Inst. 52:921-930), a SCID mouse, a thymectomized mouse, or an
irradiated mouse
(see, e.g., Bradley, et al. (1978) Br. J. Cancer 38:263-272; Selby, et al.
(1980) Br. J. Cancer
41:52-61) can be used as a host. Transplantable tumor cells (typically about
106 cells) injected
into isogenic hosts will produce invasive tumors in a high proportions of
cases, while normal
cells of similar origin will not. In hosts which developed invasive tumors,
cells expressing a
cancer-associated sequences are injected subcutaneously. After a suitable
length of time,
preferably 4-8 weeks, tumor growth is measured (e.g., by volume or by its two
largest
dimensions) and compared to the control. Tumors that have statistically
significant reduction
(using, e.g., Student's T test) are said to have inhibited growth.
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Polynucleotide modulators of cancer
Antisense and RNAi Polynucleotides
In certain embodiments, the activity of a cancer-associated protein is down-
regulated, or
entirely inhibited, by the use of an inhibitory or antisense polynucleotide,
e.g., a nucleic acid
complementary to, and which can preferably hybridize specifically to, a coding
mRNA nucleic
acid sequence, e.g., a cancer protein mRNA, or a subsequence thereof. Binding
of the antisense
polynucleotide to the mRNA reduces the translation andlor stability of the
mRNA.
In the context of this invention, antisense polynucleotides can comprise
naturally-
occurring nucleotides, or synthetic species formed from naturally-occurnng
subunits or their
close homologs. Antisense polynucleotides may also have altered sugar moieties
or inter-sugar
linkages. Exemplary among these are the phosphorothioate and other sulfur
containing species.
Analogs are comprehended by this invention so long as they function
effectively to hybridize
with the cancer protein mRNA. See, e.g., Isis Pharmaceuticals, Carlsbad, CA;
Sequitur, Inc.,
Natick, MA.
Such antisense polynucleotides can readily be synthesized using recombinant
means, or
can be synthesized in vitro. Equipment for such synthesis is sold by several
vendors, including
Applied Biosystems. The preparation of other oligonucleotides such as
phosphorothioates and
alkylated derivatives is also well known.
Antisense molecules as used herein include antisense or sense
oligonucleotides. Sense
oligonucleotides can, e.g., be employed to block transcription by binding to
the anti-sense
strand. The antisense and sense oligonucleotide comprise a single-stranded
nucleic acid
sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA
(antisense)
sequences for cancer molecules. A preferred antisense molecule is for a cancer
sequences in the
Tables, or for a ligand or activator thereof. Antisense or sense
oligonucleotides, according to
the present invention, comprise a fragment generally at least about 14
nucleotides, preferably
from about 14-30 nucleotides. The ability to derive an antisense or a sense
oligonucleotide,
based upon a cDNA sequence encoding a given protein is described in, e.g.,
Stein and Cohen
(1988) Cancer Res. 48:2659-2668; and van der Krol, et al. (1988) BioTechniques
6:958-976.
RNA interference is a mechanism to suppress gene expression in a sequence
specific
manner. See, e.g., Brumelkamp, et al. (2002) Sciencexpress (2lMarch2002);
Sharp (1999)
Genes Dev. 13:139-141; and Cathew (2001) Curr. Op. Cell Biol. 13:244-248. In
mammalian
cells, short, e.g., 21 nt, double stranded small interfering RNAs (siRNA) have
been shown to be
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effective at inducing an RNAi response. See, e.g., Elbashir, et al. (2001)
Nature 411:494-498.
The mechanism may be used to downregulate expression levels of identified
genes, e.g.,
treatment of or validation of relevance to disease.
Ribozymes
In addition to antisense polynucleotides, ribozymes can be used to target and
inhibit
transcription of cancer-associated nucleotide sequences. A ribozyme is an RNA
molecule that
catalytically cleaves other RNA molecules. Different kinds of ribozymes have
been described,
including group I ribozymes, hammerhead ribozyrnes, hairpin ribozymes, RNase
P, and axhead
ribozymes (see, e.g., Castanotto, et al. (1994) Adv. in Pharmacology 25: 289-
317 for a general
review of the properties of different ribozymes).
The general features of hairpin ribozymes are described, e.g., in Hampel, et
al. (1990)
Nucl. Acids Res. 18:299-304; European Patent Publication No. 0 360 257; U.S.
Patent No.
5,254,678. Methods of preparation are described in, e.g., WO 94/26877; Ojwang,
et al. (1993)
Proc. Natl. Acad. Sci. USA 90:6340-6344; Yamada, et al. (1994) Human Gene
Therapy 1:39-
45; Leavitt, et a1.(1995) Proc. Natl. Acad. Sci. USA 92:699-703; Leavitt, et
al. (1994) Human
Gene Theratw 5:1151-120; and Yamada, et al. (1994) Virolo~y 205: 121-126.
Polynucleotide modulators of cancer may be introduced into a cell containing
the target
nucleotide sequence by formation of a conjugate with a ligand binding
molecule, as described in
WO 91/04753. Suitable ligand binding molecules include, but are not limited
to, cell surface
receptors, growth factors, other cytokines, or other ligands that bind to cell
surface receptors.
Preferably, conjugation of the ligand binding molecule does not substantially
interfere with the
ability of the ligand binding molecule to bind to its corresponding molecule
or receptor, or
block entry of the sense or antisense oligonucleotide or its conjugated
version into the cell.
Alternatively, a polynucleotide modulator of cancer may be introduced into a
cell containing the
target nucleic acid sequence, e.g., by formation of an polynucleotide-lipid
complex, as described
in WO 90/10448. It is understood that the use of antisense molecules or knock
out and knock in
models may also be used in screening assays as discussed above, in addition to
methods of
treatment.
Thus, in one embodiment, methods of modulating cancer in cells or organisms
are
provided. In one embodiment, the methods comprise administering to a cell an
anti-cancer
antibody that reduces or eliminates the biological activity of an endogenous
cancer protein.
Alternatively, the methods comprise administering to a cell or organism a
recombinant nucleic
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acid encoding a cancer protein. This may be accomplished in any number of
ways. In a
preferred embodiment, e.g., when the cancer sequence is down-regulated in
cancer, such state
may be reversed by increasing the amount of cancer gene product in the cell.
This can be
accomplished, e.g., by overexpressing the endogenous cancer gene or
administering a gene
encoding the cancer sequence, using known gene-therapy techniques. In a
preferred
embodiment, the gene therapy techniques include the incorporation of the
exogenous gene using
enhanced homologous recombination (EHR), e.g., as described in PCT/US93/0386.
Alternatively, e.g., when the cancer sequence is up-regulated in cancer, the
activity of the
endogenous cancer gene is decreased, e.g., by the administration of a cancer
antisense or other
inhibitor, e.g., RNAi.
In one embodiment, the cancer proteins of the present invention may be used to
generate
polyclonal and monoclonal antibodies to cancer proteins. Similarly, the cancer
proteins can be
coupled, using standard technology, to affinity chromatography columns. These
columns may
then be used to purify cancer antibodies useful for production, diagnostic, or
therapeutic
purposes. In a preferred embodiment, the antibodies are generated to epitopes
unique to a
cancer protein; that is, the antibodies show little or no cross-reactivity to
other proteins. The
cancer antibodies may be coupled to standard affinity chromatography columns
and used to~
purify cancer proteins. The antibodies may also be used as blocking
polypeptides, as outlined
above, since they will specifically bind to the cancer protein.
Methods of identifying variant cancer-associated sequences
Without being bound by theory, expression of various cancer sequences is
correlated
with cancer. Accordingly, disorders based on mutant or variant cancer genes
may be
determined. In one embodiment, the invention provides methods for identifying
cells
containing variant cancer genes, e.g., determining all or part of the sequence
of at least one
endogenous cancer gene in a cell. In a preferred embodiment, the invention
provides methods
of identifying the cancer genotype of an individual, e.g., determining all or
part of the sequence
of at least one cancer gene of the individual. This is generally done in at
least one tissue of the
individual, and may include the evaluation of a number of tissues or different
samples of the
same tissue. The method may include comparing the sequence of the sequenced
cancer gene to
a known cancer gene, e.g., a wild-type gene.
The sequence of all or part of the cancer gene can then be compared to the
sequence of a
known cancer gene to determine if any differences exist. This can be done
using known


CA 02459219 2004-03-17
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homology programs, such as Bestfit, etc. In a preferred embodiment, the
presence of a
difference in the sequence between the cancer gene of the patient and the
known cancer gene
correlates with a disease state or a propensity for a disease state, as
outlined herein.
In a preferred embodiment, the cancer genes are used as probes to determine
the number
of copies of the cancer gene in the genome.
In another preferred embodiment, the cancer genes are used as probes to
determine the
chromosomal localization of the cancer genes. Information such as chromosomal
localization
finds use in providing a diagnosis or prognosis in particular when chromosomal
abnormalities
such as translocations, and the like are identified in the cancer gene locus.
Administration of pharmaceutical and vaccine compositions
In one embodiment, a therapeutically effective dose of a cancer protein or
modulator
thereof, is administered to a patient. By "therapeutically effective dose"
herein is meant a dose
that produces effects for which it is administered. The exact dose will depend
on the purpose of
the treatment, and will be ascertainable using known techniques. See, e.g.,
Ansel, et al. (1999)
Pharmaceutical Dosage Forms and Drug Delivery Lippincott; Lieberman (1992)
Pharmaceutical
Dosa= a Forms (vols. 1-3) Dekker, ISBN 0824770846, 082476918X, 0824712692,
0824716981;
Lloyd (1999) The Art, Science and Technolo~y of Pharmaceutical Compounding
Amer.
Pharmaceut. Assn.; and Pickar (1998) Dosa ,e Calculations Thomson. Adjustments
for cancer
degradation, systemic versus localized delivery, and rate of new protease
synthesis, as well as
the age, body weight, general health, sex, diet, time of administration, drug
interaction and the
severity of the condition may be necessary. U.S. Patent Application No.
09/687,576, further
discloses the use of compositions and methods of diagnosis and treatment in
cancer.
A "patient" for the purposes of the present invention includes both humans and
other
animals, particularly mammals. Thus the methods are applicable to both human
therapy and
veterinary applications. In the preferred embodiment the patient is a mammal,
preferably a
primate, and in the most preferred embodiment the patient is human.
The administration of the cancer proteins and modulators thereof of the
present
invention can be done in a variety of ways, including, but not limited to,
orally, subcutaneously,
intravenously, intranasally, transdermally, intraperitoneally,
intramuscularly, intrapulmonary,
vaginally, rectally, or intraocularly. In some instances, e.g., in the
treatment of wounds and
inflammation, the cancer proteins and modulators may be directly applied as a
solution or spray.
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The pharmaceutical compositions of the present invention comprise a cancer
protein in a
form suitable for administration to a patient. In the preferred embodiment,
the pharmaceutical
compositions are in a water soluble form, such as being present as
pharmaceutically acceptable
salts, which is meant to include both acid and base addition salts.
"Pharmaceutically acceptable
acid addition salt" refers to those salts that retain the biological
effectiveness of the free bases
and that are not biologically or otherwise undesirable, formed with inorganic
acids such as
hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric
acid, and the,like, and
organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic
acid, oxalic acid, malefic
acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid,
benzoic acid, cirmamic
acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-
toluenesulfonic acid, salicylic
acid, and the like. "Pharmaceutically acceptable base addition salts" include
those derived from
inorganic bases such as sodium, potassium, lithium, ammonium, calcium,
magnesium, iron,
zinc, copper, manganese, aluminum salts, and the like. Particularly preferred
are the
ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from
pharmaceutically acceptable organic non-toxic bases include salts of primary,
secondary, and
tertiary amines, substituted amines including naturally occurring substituted
amines, cyclic
amines and basic ion exchange resins, such as isopropylamine, trimethylamine,
diethylamine,
triethylamine, tripropylamine, and ethanolamine.
The pharmaceutical compositions may also include one or more of the following:
carrier
proteins such as serum albumin; buffers; fillers such as microcrystalline
cellulose, lactose, corn
and other starches; binding agents; sweeteners and other flavoring agents;
coloring agents; and
polyethylene glycol.
The pharmaceutical compositions can be administered in a variety of unit
dosage forms
depending upon the method of administration. For example, unit dosage forms
suitable for oral
administration include, but are not limited to, powder, tablets, pills,
capsules and lozenges. It is
recognized that cancer protein modulators (e.g., antibodies, antisense
constructs, ribozymes,
small organic molecules, etc.) when administered orally, should be protected
from digestion.
This is typically accomplished either by complexing the molecules) with a
composition to
render it resistant to acidic and enzymatic hydrolysis, or by packaging the
molecules) in an
appropriately resistant carrier, such as a liposome or a protection barrier.
Means of protecting
agents from digestion are available.
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The compositions for administration will commonly comprise a cancer protein
modulator dissolved in a pharmaceutically acceptable carrier, preferably an
aqueous carrier. A
variety of aqueous Garners can be used, e.g., buffered saline and the like.
These solutions are
sterile and generally free of undesirable matter. These compositions may be
sterilized by
conventional, well known sterilization techniques. The compositions may
contain
pharmaceutically acceptable auxiliary substances as required to approximate
physiological
conditions such as pH adjusting and buffering agents, toxicity adjusting
agents, and the like,
e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride,
sodium lactate, and
the like. The concentration of active agent in these formulations can vary
widely, and will be
selected primarily based on fluid volumes, viscosities, body weight, and the
like in accordance
with the particular mode of administration selected and the patient's needs
(e.g., (1980)
Remin~ton's Pharmaceutical Science (18th ed.) Mack, and Hardman and Limbird
(eds. 2001)
Goodman and Gilman: The Pharmacolo~ial Basis of Therapeutics (10th ed.) McGraw-
Hill.
Thus, a typical pharmaceutical composition for intravenous administration
would be
about 0.1 to 10 mg per patient per day. Dosages from 0.1 up to about 100 mg
per patient per
day may be used, particularly when the drug is administered to a secluded site
and not into the
blood stream, such as into a body cavity or into a lumen of an organ.
Substantially higher
dosages are possible in topical administration. Actual methods for preparing
parenterally
administrable compositions will be known or apparent.
The compositions containing modulators of cancer proteins can be administered
for
therapeutic or prophylactic treatments. In therapeutic applications,
compositions are
administered to a patient suffering from a disease (e.g., a cancer) in an
amount sufficient to cure
or at least partially arrest the disease and its complications. An amount
adequate to accomplish
this is defined as a "therapeutically effective dose." Amounts effective for
this use will depend
upon the severity of the disease and the general state of the patient's
health. Single or multiple
administrations of the compositions may be administered depending on the
dosage and
frequency as required and tolerated by the patient. In any event, the
composition should
provide a sufficient quantity of the agents of this invention to effectively
treat the patient. An
amount of modulator that is capable of preventing or slowing the development
of cancer in a
mammal is referred to as a "prophylactically effective dose." The particular
dose required for a
prophylactic treatment will depend upon the medical condition and history of
the mammal, the
particular cancer being prevented, as well as other factors such as age,
weight, gender,
78


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
administration route, efficiency, etc. Such prophylactic treatments may be
used, e.g., in a
mammal who has previously had cancer to prevent a recurrence of the cancer, or
in a mammal
who is suspected of having a significant likelihood of developing cancer
based, at least in part,
upon gene expression profiles. Vaccine strategies may be used, in either a DNA
vaccine form,
or protein vaccine.
It will be appreciated that the present cancer protein-modulating compounds
can be
administered alone or in combination with additional cancer modulating
compounds or with
other therapeutic agent, e.g., other anti-cancer agents or treatments.
In numerous embodiments, one or more nucleic acids, e.g., polynucleotides
comprising
nucleic acid sequences set forth in the Tables, such as RNAi, antisense
polynucleotides or
ribozymes, will be introduced into cells, in vitro or in vivo. The present
invention provides
methods, reagents, vectors, and cells useful for expression of cancer-
associated polypeptides
and nucleic acids using in vitro (cell-free), ex vivo or in vivo (cell or
organism-based)
recombinant expression systems.
The particular procedure used to introduce the nucleic acids into a host cell
for
expression of a protein or nucleic acid is application specific. Many
procedures for introducing
foreign nucleotide sequences into host cells may be used. These include the
use of calcium
phosphate transfection, spheroplasts, electroporation, liposomes,
microinjection, plasma
vectors, viral vectors, and other well known methods for introducing cloned
genomic DNA,
cDNA, synthetic DNA, or other foreign genetic material into a host cell (see,
e.g., Berger and
I~immel (1987) Guide to Molecular Cloning Techniques from Methods in
Enzymolo~y (vol.
152) Academic Press; Ausubel, et al. (eds. 1999 and supplements) Current
Protocols Lippincott;
and Sambrook, et al. (2001) Molecular Cloning: A Laboratory Manual (3d ed.,
Vol. 1-3) CSH
Press.
In a preferred embodiment, cancer proteins and modulators are administered as
therapeutic agents, and can be formulated as outlined above. Similarly, cancer
genes (including
both the full-length sequence, partial sequences, or regulatory sequences of
the cancer coding
regions) can be administered in a gene therapy application. These cancer genes
can include
inhibitory applications, e.g., as inhibitory RNA, gene therapy (e.g., for
incorporation into the
genome), or antisense compositions.
Cancer polypeptides and polynucleotides can also be administered as vaccine
compositions to stimulate HTL, CTL, and antibody responses. Such vaccine
compositions can
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CA 02459219 2004-03-17
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include, e.g., lipidated peptides (see, e.g.,Vitiello, et al. (1995) J. Clin.
Invest. 95:341-349),
peptide compositions encapsulated in poly(DL-lactide-co-glycolide) ("PLG")
microspheres
(see, e.g., Eldridge, et al. (1991) Molec. Immunol. 28:287-294,; Alonso, et
al. (1994) Vaccine
12:299-306; Jones, et al. (1995) Vaccine 13:675-681), peptide compositions
contained in
immune stimulating complexes (ISCOMS) (see, e.g., Takahashi, et al. (1990)
Nature 344:873-
875; Hu, et al. (1998) Clin Ex~ Immunol. 113:235-243), multiple antigen
peptide systems
(MAPS) (see, e.g., _Tam (1988) Proc. Natl. Acad. Sci. USA 85:5409-5413; Tam
(1996) J.
Immunol. Methods 196:17-32), peptides formulated as multivalent peptides;
peptides for use in
ballistic delivery systems, typically crystallized peptides, viral delivery
vectors (Perkus, et al., p.
379, in Kaufinann (ed. 1996) Concerts in Vaccine Development de Gruyter;
Chakrabarti, et al.
(1986) Nature 320:535-537; Hu, et al. (1986) Nature 320:537-540; Kieny, et al.
(1986)
Bio/Technolo~y 4:790-795; Top, et al. (1971) J. Infect. Dis. 124:148-154;
Chanda, et al. (1990)
Virolo~y 175:535-547), particles of viral or synthetic origin (see, e.g.,
Kofler, et al. (1996) J.
Immunol. Methods 192:25-35; Eldridge, et al. (1993) Sem. Hematol. 30:16-24;
Falo, et al.
(1995) Nature Med. 1:649-653), adjuvants (Warren, et al. (1986) Annu. Rev.
Immunol. 4:369-
388; Gupta, et al. (1993) Vaccine 11:293-306), liposomes (Reddy, et al. (1992)
J. Immunol.
148:1585-1589; Rock (1996) Immunol. Today 17:131-137), or, naked or particle
absorbed
cDNA (Ulmer, et al. (1993) Science 259:1745-1749; Robinson, et al. (1993)
Vaccine 11:957-
960; Shiver, et al., p 423, in Kaufmann (ed. 1996) Concepts in Vaccine
Development de
Gruyter; Cease and Berzofsky (1994) Annu. Rev. Immunol. 12:923-989; and
Eldridge, et al.
(199 Sem. Hematol. 30:16-24). Toxin-targeted delivery technologies, also known
as receptor
mediated targeting, such as those of Avant Immunotherapeutics, Inc. (Needham,
Massachusetts)
may also be used.
Vaccine compositions often include adjuvants. Many adjuvants contain a
substance
designed to protect the antigen from rapid catabolism, such as aluminum
hydroxide or mineral
oil, and a stimulator of immune responses, such as lipid A, Bortadella
pertussis, or
Mycobacterium tuberculosis derived proteins. Certain adjuvants are
commercially available as,
e.g., Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories,
Detroit, MI);
Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ); AS-2 (SmithKline
Beecham,
Philadelphia, PA); aluminum salts such as aluminum hydroxide gel (alum) or
aluminum
phosphate; salts of calcium, iron, or zinc; an insoluble suspension of
acylated tyrosine; acylated
sugars; cationically or anionically derivatized polysaccharides;
polyphosphazenes;


CA 02459219 2004-03-17
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biodegradable microspheres; monophosphoryl lipid A and quil A. Cytokines, such
as GM-CSF,
interleukin-2, -7, -12, and other like growth factors, may also be used as
adjuvants.
Vaccines can be administered as nucleic acid compositions wherein DNA or RNA
encoding one or more of the polypeptides, or a fragment thereof, is
administered to a patient.
This approach is described, for instance, in Wolff et. al. (1990) Science
247:1465-1468, as well
as U.S. Patent Nos. 5,580,859; 5,589,466; 5,804,566; 5,739,118; 5,736,524;
5,679,647; WO
98/04720; and in more detail below. Examples of DNA-based delivery
technologies include
"naked DNA", facilitated (bupivicaine, polymers, peptide-mediated) delivery,
cationic lipid
complexes, and particle-mediated ("gene gun") or pressure-mediated delivery
(see, e.g., U.S.
Patent No. 5,922,687).
For therapeutic or prophylactic immunization purposes, the peptides of the
invention can
be expressed by viral or bacterial vectors. Examples of expression vectors
include attenuated
viral hosts, such as vaccinia or fowlpox. This approach involves the use of
vaccinia virus, e.g.,
as a vector to express nucleotide sequences that encode cancer polypeptides or
polypeptide
fragments. Upon introduction into a host, the recombinant vaccinia virus
expresses the
immunogenic peptide, and thereby elicits an immune response. Vaccinia vectors
and methods
useful in immunization protocols are described in, e.g., U.S. Patent No.
4,722,848. Another
vector is BCG (Bacille Calmette Guerin). BCG vectors are described in Stover,
et al. (1991)
Nature 351:456-460. A wide variety of other vectors are availablel for
therapeutic
administration or immunization, e.g., adeno and adeno-associated virus
vectors, retroviral
vectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, and the
like. See, e.g.,
Shata, et al. (2000) Mol Med Today 6:66-71; Shedlock, et al. (2000) J. Leukoc.
Biol. 68:793-
806; Hipp, et al. (2000) In Vivo 14:571-85.
Methods for the use of genes as DNA vaccines are well known, and include
placing a
cancer gene or portion of a cancer gene under the control of a regulatable
promoter or a tissue-
specific promoter for expression in a cancer patient. The cancer gene used for
DNA vaccines
can encode full-length cancer proteins, but more preferably encodes portions
of the cancer
proteins including peptides derived from the cancer protein. In one
embodiment, a patient is
immunized with a DNA vaccine comprising a plurality of nucleotide sequences
derived from a
cancer gene. For example, cancer-associated genes or sequence encoding
subfragments of a
cancer protein axe introduced into expression vectors and tested for their
immunogenicity in the
context of Class I MHC and an ability to generate cytotoxic T cell responses.
This procedure
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provides for production of cytotoxic T cell responses against cells which
present antigen,
including intracellular epitopes.
In a preferred embodiment, DNA vaccines include a gene encoding an adjuvant
molecule with the DNA vaccine. Such adjuvant molecules include cytokines that
increase the
immunogenic response to the cancer polypeptide encoded by the DNA vaccine.
Additional or
alternative adjuvants are available.
In another preferred embodiment, cancer genes find use in generating animal
models of
cancer. When the cancer gene identified is repressed or diminished in cancer
tissue, gene
therapy technology, e.g., wherein inhibitory or antisense RNA directed to the
cancer gene will
also diminish or repress expression of the gene. Animal models of cancer fmd
use in screening
for modulators of a cancer-associated sequence or modulators of cancer.
Similarly, transgenic
animal technology, including gene knockout technology, e.g., as a result ~of
homologous
recombination with an appropriate gene targeting vector, will result in the
absence or increased
expression of the cancer protein. When desired, tissue-specific expression or
knockout of the
cancer protein may be necessary.
It is also possible that the cancer protein is overexpressed in cancer. As
such, transgenic
animals can be generated that overexpress the cancer protein. Depending on the
desired
expression level, promoters of various strengths can be employed to express
the transgene.
Also, the number of copies of the integrated transgene can be determined and
compared for a
determination of the expression level of the transgene. Animals generated by
such methods will
find use as animal models of cancer and are additionally useful in screening
for modulators to
treat cancer.
Kits for Use in Diagnostic and/or Prognostic Applications
For use in diagnostic, research, and therapeutic applications suggested above,
kits are
also provided by the invention. In diagnostic and research applications, such
kits may include
at least one of the following: assay reagents, buffers, cancer-specific
nucleic acids or antibodies,
hybridization probes and/or primers, antisense polynucleotides, ribozymes,
dominant negative
cancer polypeptides or polynucleotides, small molecule inhibitors of cancer-
associated
sequences etc. A therapeutic product may include sterile saline or another
pharmaceutically
acceptable emulsion and suspension base.
Iii addition, the kits may include instructional materials containing
instructions (e.g.,
protocols) for the practice of the methods of this invention. While the
instructional materials
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typically comprise written or printed materials, they are not limited to such.
A medium capable
of storing such instructions and communicating them to an end user is
contemplated by this
invention. Such media include, but are not limited to, electronic storage
media (e.g., magnetic
discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like.
Such media may
include addresses to Internet sites that provide such instructional materials.
The present invention also provides for kits for screening for modulators of
cancer-
associated sequences. Such kits can be prepared from readily available
materials and reagents.
For example, such kits can comprise one or more of the following materials: a
cancer-associated
polypeptide or polynucleotide, reaction tubes, and instructions for testing
cancer-associated
activity. Optionally, the kit contains biologically active cancer protein. A
wide variety of kits
and components can be prepared according to the present invention, depending
upon the
intended user of the kit and the particular needs of the user. Diagnosis would
typically involve
evaluation of a plurality of genes or products. The genes will typically be
selected based on
correlations with important parameters in disease which may be identified in
historical or
outcome data.
EXAMPLES
Example 1: Gene Chip Analysis
Molecular profiles of various normal and cancerous tissues were determined and
analyzed using gene chips. RNA was isolated and gene chip analysis was
performed as
described (Glynne, et al. (2000) Nature 403:672-676; Zhao, et al. (2000) Genes
Dev. 14:981-
993).
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Table 1 lists medical conditions, abnormalifies, or organs affected by
disease, referred to in Tables 2A-68, for which markers have been idenfified,
and other related medical
conditions (including various stages andlor metastases) in which those markers
will also be useful, e.g., in therapeutic, diagnosfic, prognostic, subsetting,
vaccine, and other uses.
blood vesselslangiogenesis: hemangiomas, lymphangiomas, wound healing, tissue
remodeling, psoriasis, ischemic, heart disease, inflammatory diseases (e.g.,
arfhrifis, asthma,
chronic bronchitis), alherosclerosis, endometriosis, presumed ocular
histoplasmosis syndrome, hypoxia, solid tumors, lymphomas, autoimmune diseases
(e.g., RA, SLE, juvenile
chronic arthritis, pigmented villonodular synovifis, etc.), retinal
neovascularization syndromes (e.g., diabetic refinopathy, macular
degenerafion, presumed ocular histoplasmosis
syndrome, etc.), scleritislconjunctivitis, hyperirophic scars (keloid), birth
control, uterine fibroids
bladder. carcinoma in situ, papillary carcinomas, Uansitional cell carcinoma
bone marrow: Ewing sarooma, sarcomas arising from skeletal and extraskeletal
connecfive fissues, including the peripheral nervous system
1 ~ brain: glioblastoma, oligodendroglioma, anablasfic astrocytoma,
meningioma, medulablastoma, neuroblastoma, ependymoma, schwannoma,
craniopharyngioma, pineoblastoma,
pineocytoma
breast: ductal caroinoma in situ, lobular carcinoma in situ
cervix: cancer of the cervix, vagina, or vulva
colonlrectum: precancerous colorectal disease (e.g., neoplasfic polyps
(adenomas), familial adenomatous poiyposis, ulcerative colitis), colon cancer,
e.g., epithelial tumor (e.g.,
I S adenocarcinoma, mutinous adenocaroinoma, signet-ring cell adenocarcinoma,
squamcus cell carcinoma, adenosquamous carcinoma, undifferentiated caroinoma,
unclassified
carcinoma), carinoid tumor (e.g., argenta~n, nonargentaffin, composite), non-
epithelial tumor (e.g., leimyo sarcroma, others), inflammatory bowel disease
(e.g., ulcerafive colifis,
Crohn's disease (granulomatous colitis), dysplasia), rectal cancer, cancer of
the anal region (e.g., squamous cell caroinoma, transifional caroinoma,
adenocaroinoma, carcinoma,
papillary villous caroinoma, mutinous adenocarcinoma, melanoma)
2o esophagus: premalignant or predisposing conditions (e.g., esophagifis),
squamous cell cancers (e.g., cancers of the head and neck, lung, or cervix),
gastrodigestive carcinomas
(e.g., cancers of the stomach, colon, or rectum)
fibrosis: lung fibrosis (idiopathic pulmonary fibrosis, hypersensitivity
pneumonitis,interstitiat pneumonifis, nonspecific idiopathic pneumonifis),
chronic obstructive pulmonary disease
(e.g., emphysema, chronic bronchifis), asthma, bronchiectasis, cirrhosis
(liver fibrosis), renal fibrosis, sclerodertna, wound healing
head and neck: tumors of the nasal cavity, paranasal sinuses, nasopharynx,
oral cavity, oral pharynx, lip, larynx, hypopharynx, salivary glands,
paragangliomas, esophagus
kidney: clear cell (nonpapillary) carcinoma, papillary carcinoma, chromophobe
renal carcinoma, hypemephroma, adenocaroinoma, sporadic renal carcinomas,
hereditary renal
carcinomas (von Hippei-Lindau disease), carcinoma pf the renal pelvis,
ureteral carcinoma, fibroma, papillary adenoma, angiomyolipoma, oncocytoma
leukocytes: acute lymphoblastic leukemiallymphoma, malignant transformafion of
immature, precursor B (pre-B) or precursor T (pre-T) lymphocytes, or
lymphoblasts, arthrifis,
inflammation, wound healing
liver: hepatitis (e.g., types A, B, C), benign epithelial tumors and tumor
bile condifions, primary malignant epithelial tumors, primary malignant
mesenchymal tumors, tumors of the
gallbladder or bile duct
30 lung: lung cancer, small cell lung carcinoma (oat cell carcinoma), non-
small cell carcinomas (e.g., squamous cell carcinoma, adenocarcinoma, large
cell lung carcinoma, carcinoid,
granulomatous), fibrosis (idiopathic pulmonary fibrosis, hypersensitivity
pneumonitis,interstifial pneumonilis, nonspecific idiopathic pneumonitis),
chronic obstructive pulmonary
disease (e.g., emphysema, chronic bronchifis), asthma, bronchiectasis,
esophageal cancer
ovary: ovarian carcinoma (e.g., epithelial (serous tumors, mutinous tumors,
endometrioid tumors), germ cell (e.g., teratomas, choriocarcinomas,
polyembryomas, embryomal
carcinoma, endodermal sinus tumor, dysgerminoma, gonadoblasloma), stromal
carcinomas (e.g., granulosal stromal cell tumors)), fallopian tube carcinoma,
peritoneal carcinoma,
3 5 leiomyoma
pancreas: adenocarcinoma ductal adenocaroinoma, mutinous cyst adenocarcinoma,
acinar cell carcinoma, unclassified large cell carcinoma, small cell
carcinoma,
pancreatoblastoma, duct-ectafic mucin-hypersecreting tumor, mutinous cyst
adenoma, papillary cysfic neoplasm, serous cyst adenoma, diabetes melifis,
chronic pancreatifis
prostate: epithelial neoplasms (e.g., adenocarcinoma, small cell tumors,
transitional cell carcinoma, caroinoma in situ, and basal cell carcinoma),
caroinosarcoma non-epithelial
4o neoplasms (e.g., mesenchymal and lymphoma), germ cell tumors, prostatic
intraepithelial neoplasia (PIN), hormone independent prostate cancer, benign
prostate hyperplasia,
prostatitis
skin/melanoma: melanoma, lentigo (common benign localized hyperplasia of
melanocytes), nevocellular nevi (congenital or acquired neoplasm of
melanocytes), acfinic keratosis
(overgrowth of outer layers of skin), basal cell carcinoma, Merkel cell
carcinoma, benign fibrous hisfiocyloma (dermal neoplasms of fibroblasts and
histiocytes),
dermatofibrosarcoma protuberans (well differentiated fibrosarcoma of the
skin), xanthomas (tumor-like collecfions of foamy his6ocytes within the
dertnis), dermal vascular tumors,
seborrheic keratoses (benign tumor), acanthosis nigricans (benign or malignant
hyperplasia and hyperpigmentation of skin), and squamous cell carcinomas of
the skin, lung,
45 cervix, esophagus, uterus, head, neck, or bladder
stomach: adenocarcinoma, squamous cell caroinoma, adenoacanthoma, caroinoid,
leiomyosarcoma, gastritis (chronic atrophic, H. pylori associated),
hyperplasfic polyps, lipoma,
leiomyoma, esophageal adenocarcinomas
testicles: germ cell tumors (including seminomas, embryonal carcinomas,
teratomas, choriocarcinomas, yolk sac tumors), sex chord stromal tumors
(including Leydig cell tumors,
Sertoli cell tumors, and Granulosa cell tumors), germ cell and gonadal stromal
elements (e.g., gonadoblastomas), adnexal and paratesticular tumors (e.g.,
mesotheliomas, soff
tissue sarcomas, and adnexal of the rete testes), miscellaneous necplasms
(including carcinoid, lymphoma, and cysts)
uterus: epithelial tumors (e.g., endometrioid, papillary endometrioid,
papillary serous, clear cell, mutinous), mesenchymal tumors (e.g., endometrial
stromal sarooma,
leiomyosarcoma, nonspecific saroomas), mixed tumors (e.g., malignant mixed
mullerian tumors, adenosarcoma)
5 Tables 2B-66C list accession numbers for Pkeys lacking UnigenelD's for
Tables 2A-66C, respecfively. For each probeset is listed gene cluster number
from which oligonucleotides
were designed. Gene clusters were compiled using sequences derived from
Genbank ESTs and mRNAs. These sequences were clustered based on sequence
similarity using
Clustering and Alignment Tools (DoubIeTwist, Oakland California). Genbank
accession numbers for sequences comprising each cluster are listed in the
°Accession" column.
6o Tables 2G66C list genomic positioning for Pkeys lacking Unigene ID's and
accession numbers in Tables 2A-66C, respectively. For each predicted exon is
listed genomic sequence
source used for prediction. Nucleotide locafions of each predicted exon are
also listed.
TABLE 2A: ABOUT 1031 GENES UP-REGULATED IN ACUTE LYMPHOCYTIC LEUKEMIA (ALL)
Table 2A lists about 1031 genes up-regulated in acute lymphocyfic leukemia
(ALL) compared to normal adult tissues. These were selected from 35403
probesets on the
AftymetrixlEos Hu01 GeneChip array such that the ratio of "average" leukemia
to "average" normal adult tissues was greater than or equal to 1.7. The
"average" leukemia level was
set to the 75"~ percentile amongst various ALL samples. The "average" normal
adult tissue level was set to the 85"~ peroentile amongst various non-
malignant fissues. In order to
remove gene-specific background levels of non-specific hybridization, the
7.5'" percentile value amongst various non-malignant tissues was subtracted
from both the numerator and
the denominator before the ratio was evaluated.
Pkey: Unique Eos probeset idenfifier number
ExAccn: Exemplar Accession number, Genbank accession number
7o UnigenelD: Unigene number
Unigene Title: Unigene gene title
R1: Ratio of leukemia to normal body tissue

Pkey ExAccUniGeneIDUniGeneTifie R1


75 100458S74019Hs.247979pre-B lymphocyte gene46.8
1


113089 T40707Hs.270862ESTs 20.4


106956 806428Hs.226351ESTs 15.8


101447 M21305 gb:Human alpha satellite13.8
and satellite 3


113009 T23699Hs.7246ESTs 12.5


126947 240778Hs.191837ESTs 11.4


100893 BE245294Hs.180789S164 protein 11.1


101050 AU077324Hs.1832neurapeptideY 11.0


132114 NM_006152Hs.40202lymphoid-restricted 10.7
membrane protein


~4


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
101304AA001021Hs.6685thyroid hormone receptor10.4
interaclor 8


105667AA767526Hs.22030paired box gene 5 (Bell9.1
lineage specif


112727791029Hs.15069ESTs 9.0


109788779971Hs.12432Homo Sapiens clone 8.7
24407 mRNA sequence


113374779925Hs.269165ESTs, Weakly similar 7.8
to ALU1 HUMAN ALU
5


130466W19744Hs.180059Homo Sapiens cDNA FLJ206537.7
fis, clone KA


109384AA219172Hs.86849ESTs 7.6


112602AW004045Hs.203365ESTs 6.6


125278AI218439Hs.i29998enhancerofpolycombi 6.5


1 112167N99591Hs.25587ESTs, Weakly similar 6.4
~ to 700329 hypotheti


116355AA789133Hs.88650ESTs 5.8


123440A1733692Hs.112488ESTs 5.5


100918AK001335Hs.31137protein tyrosine phosphatase,5.4
receptor t


101879AA176374Hs.243886nuclear autoaniigenic 5.4
sperm protein (his


15 109260AW978515Ns.131915KIAA0863 protein 5.4


129213AI146494Hs.109525ESTs, Weakly similar 5.4
to IRX2 HUMAN IROQU


120809AA346495 gb:EST52657 Fetal heart5.4
II Homo Sapiens


105498H68279Hs.24937Uansformer-2 alpha 5.1
(hUa-2 alpha)


114840AA447591Hs.87359ESTs, Highly similar 5.0
to RB18 HUMAN RAS-R


103304BE561801Hs.2484T-cell leukemiallymphoma4.9
1A


113983W87415Hs.55296HLA-B associated Uanscript-14.8


115844AI373062Hs.332938hypothetical protein 4.8
MGC5370


120712AF193339Hs.102506eukaryotic translation4.8
initiation factor


107794AA019255 gb:ze56e10.s15oares 4.7
retina N2b4HR Homo


25 135101U82275Hs.94498leukocyte immunoglobulin-like4.6
receptor,


129898AI672731Hs.i3256ESTs 4.6


113494791451Hs.86538ESTs 4.6


115004AA329340Hs.4867mannosyl (alpha-1,3-)-glycoprotein4.5
beta-


113074AK001335Hs.31137protein tyrosine phosphatase,4.5
receptor t


112326855822Hs.4268ESTs 4.4


105169BE245294Hs.180789S164 protein 4.4


117048H89732Hs.230113EST 4.3


123133AA487264Hs.154974Homo sapiens mRNA; 4.3
cDNA DKFZp667N064
(fr


111394AA412227Hs.16131hypothetical protein 4.3
FLJ12876


35 106112AL117518Hs.3686KIAA0978 protein 4.2


114414AW152166Hs.182113ESTs 4.2


125219AI804331Hs.99423ATP-dependent RNA helicase4.2


114995AA769266Hs.193657ESTs 4.2


123338AA504249Hs.187585ESTs 4.1


126666AA648886Hs.151999ESTs 4.1


112908BE281000Hs.3530TLS-associated serine-arginine4.1
protein 2


116640X89984Hs.211563B-cell CLLnymphoma 4.0
7A


109292AW975746Hs.188662KIAA1702 protein 4.0


131724AK001335Hs.31137protein tyrosine phosphatase,4.0
receptor t


45 119772AJ250839Hs.58241gene for serinelthreonine4.0
protein kinase


134453AI272141Hs.83484SRY (sex determining 4.0
region Y)-box 4


123562AA177088Hs.190065ESTs 4.0


103226X75042Hs.44313v-rel avian reticuloendotheliosis3.9
viral


127610AA960867Hs.150271ESTs, Highly similar 3.9
to unnamed protein


119873AI660149Hs.44865lymphoid enhancer-binding3.9
factor 1


115553AJ275986Hs.71414Uanscriptionfactor(SMIF3.9
gene)


131844A1419294Hs.324342ESTs 3.8


123360AA532718Hs.178604ESTs 3.8


11 A1798851Hs.283108hemoglobin, gamma G 3.8
t
160


129426AF077953Hs.111323Protein inhibitor of 3.8
5 activated STAT X


105434AA252111Hs.15200ESTs 3.8


119073BE245360Hs.279477ESTs 3.8


127003AW816515Hs.173540ATPase, Class V, type 3.7
10D


119325751136Hs.90489ESTs 3.7


115998AA448488Hs.336629ribosomal protein L44 3.7


119830AW054922Hs.53478Homo sapiens cDNA FLJ123663.7
fis, clone MA


104584AA704538Hs.193777ESTs 3.6


105212AA205334Hs.324278Homo Sapiens mRNA; 3.6
cDNA DKFZp566M063
(f


109223AW000714Hs.65818ESTs 3.6


65 112605879374Hs.29852ESTs 3.5


105733AA767669Hs.10242ESTs 3.5


120562BE244580Hs.302267hypothetical protein 3.5
FLJ10330


112268W39609Hs.22003solute tamer family 3.5
6 (neuroUansmitte


12783dAW301022Hs.337631EST 3.5


70 115147AA745781Hs.38399hypothetical protein 3.5
MGC2454


115185BE299677Hs.105461hypothetical protein 3.5
FLJ20357


113921AW976530Hs.28355hypothetical protein 3.5
FLJ22402


115835AA521410Hs.41371ESTs 3.5


123503AW975051Hs.293156ESTs, Weakly similar 3.5
to 178885 serinelth


75 128527AA504583Hs.101047Uanscription factor 3.4
3 (E2A immunoglobul


128743844284Hs.2730heterogeneous nuclearribonucleoprotein3.4


117031H88353 gb:yw21a02.s1 Morton 3.4
Fetal Cochlea Homo


123149AI734179Hs.105676ESTs 3.4


102581AU077228Hs.77256enhancer of zeste (Drosophila)3.4
homolog 2


80 103158BE242587Hs.118651hematopoietically expressed3.4
homeobox


107599AW664072Hs.60136ESTs 3.4


125556AB033064Hs.334806KIAA1238 protein 3.4


103331AI825463Hs.147996protein kinase, X-linked3.4




CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
114387AI655141Hs.107720ESTs, Weakly similar 3.4
to A54295 interfer


119040802394Hs.269436ESTs, Moderately similar3.4
to PC4259 fem


100305NM Hs.171872DEADIH (Asp-Glu-Ala-AspIHis)3.4
004941 box polypep


129818T71092Hs.172572hypothetical protein 3.3
FLJ20093


133445AC005262Hs.73797guanine nucleotide binding3.3
protein (G pr


132111AW500857Hs.40137anaphase-promoting complex3.3
1; meiotic ch


105292AF128542Hs.166846polymerase (DNA directed),3.3
epsilon


118397BE139479Hs.i61492ESTs 3.3


118922AW206193Hs.91065hypothetical protein 3.2
1 132 OKFZp761B2423
d 44


3 AW977189Hs.45719KIAA0823 protein 3.2


129889AA810932Hs.131899ESTs, Weakly similar 3,2
to T00370 hypotheti


123670AI189844Hs.112708ESTs, Moderately similar3.2
to ZN91 HUMAN Z


f AW410377Hs.d1502hypothetical protein 3,2
16291 FlJ21276


105289AB020638Hs.103000KIAA0831 protein 3,2
I
S


105583AA278907Ns.3530TLS-associated serine-arginine3,2
protein


104796BE620712Hs.33026hypothetical protein 3,2
PP2447


111657807364Hs.268667ESTs,WeaklysimilartoALU13.2
FIUMANALU


134174AF283770Hs.79630CD79A antigen (immunoglobulin-associated3.2


126077M78772Hs.210836ESTs 3.1
13


3733 AK000476Hs.75798hypotheticalprotein 3.1


124847W07701Hs.304177Homo Sapiens clone FLB85033_1
PR02286 mRNA,


127879AA768098Hs.189079ESTs 3.1


113108AW516695Hs.8438ESTs 3,1


110343AW136703Hs.17268ESTs 3.1


102935HE561850Hs.80506small nuclear ribonucleoprotein3.1
polypept


111676AB040882Hs.109778KIAA1449 protein 3,1


127311AAd92582Hs.3224Q4hypotheticalprotein 3,1
MGC4175


108830AA131743Hs.193352ESTs 3.1


1113308E247767Hs.18166KIAA0870 protein 3.1


104246AF016032Hs.201377lysosomal apyrase-like 3,1
1


126668AA011616Hs.269877ESTs 3.1


124724H20816Hs.112423Homo Sapiens mRNA; cDNA3.1
DKFZp586I1420 (f


114794AI751157Hs.101395hypothetical protein 3.1
MGC11352


(34599X99226Ns.284153Fanconi anemia, complementation3.0
35 group A


130314NM Hs.154332KIAA0212geneproduct 3.0
014674


100265D38521Hs.112396KiAA0077 protein 3.0


115005AI760825Hs.111339ESTs 3.0


123433AW450922Hs.112478ESTs 3.0


127798AA737068Hs.294078ESTs 3.0


117403H84455Hs.40639ESTs 3.0


107111A1298448Hs.22670chromodomain helicase 3,0
DNA binding protei


105698AW957300Hs.294142ESTs, Weakly similar 3.0
to C55663 oligodend


108358M81933Hs.1634cell division cycle 3.0
25A


132066AI929392Hs.181195DnaJ (Hsp40) homolog, 2.9
45 subfamily B, membe


130303BE245294Hs.180789S164 protein 2,g


104596AF067804Hs.i5423hypothetical protein 2,g
HDCMC04P


112197NM Hs.5637ESTs 2,g
003655


132809AF036144Hs.5734meningioma expressed 2,9
antigen 5 (hyaluron


100877X80821Ns.27973KIAA0874 protein 2,g


108147AI972094Hs.286221Homo Sapiens cDNA FLJ137412,9
tis, clone PL


133674AW851121Hs.75497Homo Sapiens cDNA: F1J221392.9
fis, clone H


129001AA443323Hs.107812BPOZ protein 2,g


131920BE002320Hs.287864Homo Sapiens cDNA FLJ140302.9
fis, clone HE


134709NM Hs.211600tumor necrosis factor, 2.8
55 006290 alpha-induced pro


113577AI300699Hs.278937PR00470protein 2,g


1158398E300266Hs.28935transducin-like enhancer2,g
of split 1, hom


129969N57818 gb:yv59d07.sfSoaresfetalliverspleen2,g


128659AW630087Hs.103315trinucleotiderepeatcontainingl2,g


105011BE091926Hs.16244mitotic spindle coiled-coil2,g
related prat


129294AF172940Hs.1845d2CGI-127 protein 2.8


104518H20816Hs.112423Homo sapiens mRNA; cDNA2,7
DKFZp58611420 (f


107796AA058848Hs.60797ESTs 2.7


106331A8037742Hs.2d336KIAA1321 protein 2,7


127692A1021912Hs.187983ESTs 2.7
65


131916AA025976Hs.34569ESTs 2.7


124971T23800Hs.151001hypotheticalprotein 2.7
FLJ14728


129428AA256906Hs.111364ESTs, Weakly similar 2,7
to ubiquitous TPR m


118348AW408586Hs.91052ESTs, Moderately similar2,7
to ALUS HUMAN A


113219T59257Hs.269528ESTs Moderately similar2.7
1 to ALUB-HUMAN A
1


3 268128Hs.3109Rho GTPase activating 2.7
720 protein 4


109593AW196801Hs.6685thyroid hormone receptor2,7
interactor 8


135359AF043722Hs.99491R4S guanyl releasing 2.7
protein 2 (calcium


131689AB012124Hs.30696transcription factor-like2,7
5 (basic helix


117457N29682Hs.44071ESTs Weakly similar 2.7
75 1 toALUS-HUMANALU


21073H46199Hs.112184DKFZP586J0619 protein 2.7


125069H81306Hs.194485ESTs 2,7


116456AI381911Hs.334859KIAA1814 protein 2.7


124271AW293223Hs.8928hypothetical protein 2.7
FLJ20291


112369AW966243Hs.4243hypothetical protein 2.7
FLJ12650


115866AW062629Hs.52081KIAA0867 protein 2.7


132543BE568452Hs.5101protein regulator ofcytokinesisi2.7


124494N54831Hs.271381ESTs, Weakly similar 2,7
to 138022 hypothet


104799AA029703 gb:ze95hOB.s1 Soares-fetal-heart2.7
NbHHI9W


86


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
120510AI796395Hs.111377ESTs 2.6


129781AA30fi090Hs.124707ESTs 2.6


122698AA456112Hs.9941DESTs 2.6


106995AB023139Hs.37892KIAA0922 protein 2.6


105502BE464016Hs.238956ESTs 2.6


128671A1885045Hs.211586phosphoinositide-3-kinase,2.6
regulatory s


107059BE614410Hs.23044RAD51 (S. cerevisiae) 2.6
homolog (E colt Re


126502T10077Hs.13453hypothetical protein 2.6
FLJ14753


129703BE388665Hs.179999Homo Sapiens, clone 2.6
IMAGE:3457003, mRNA


1 111219N68836Hs.19247ESTs, Moderately similar2.6
~ to ALUC-HUMAN


133529W45623Hs.74571ADP-ribosylation factor2.6
1


125626A1038854Hs.180789St64 protein 2.6


111189N67603Hs.272130ESTs, Weakly similar 2.6
to S65824 reverse


113146BE151985Hs.5722hypolheUcal protein 2.6
FLJ23316


I 125562AI494372Hs.98968hypothetical protein 2.6
S FLJ23058


102263029171Hs.75852casein kinase 1, delta 2.6


118835AA535246Hs.50852ESTs 2.fi


103141X66113Hs.75584polymyositislscleroderma2.6
autoanGgen 2 (


109598840515Hs.21248ESTs 2.fi


127262AA828125 gb:od71a09.siNCl CGAP_Ov2Homosapiens2.6


129620D79338Hs.239720CCR4-NOT transcdpfion 2.6
complex, subunit


125905Ai678638Hs.6456chaperonin containing 2.6
TCP1, subunit 2 (b


123255AA830335Hs.105273ESTs 2.6


133160N54968Hs.66309hypothetical protein 2.6
MGC11061


25 109638AW977747Hs.119120E3 ubiquilin ligase 2.6
SMURF1


119896AA731836Hs.137319ESTs 2.6


134770M89957Hs.89575CD798 antigen (immunoglobulin-associated2.6


119403AL117554Hs.119908nucleolar protein NOP51NOP582.6


129563AF119664Hs.27299transcriptional regulator2.6
protein


111719AI655806Hs.179262ESTs 2.6


103982AA218558Hs.7905sorting nexin 9 2.6


125032T74884 gb:yc58d02.s1 Stratagene2.5
liver (93722d)


131426AL122045Hs.26703CCR4-NOT transcription 2.5
complex, subunit


131938AF176085Hs.34956neural polypydmidine 2.5
tract binding prot


35 102450048251Hs.75871protein kinase C binding2.5
protein 1


133761AF041430Hs.75922brain protein 13 2.5


126339AA152106Hs.4859cyclinLania-6a 2.5


118967AI668670Hs.216756ESTs 2.5


123110AA486256Hs.193510EST 2.5


114092H81213Hs.14825ESTs, Weakly similar 2.5
to KIAA1503 protein


113247T63856Hs.193430ESTs, Weakly similar 2.5
to 2109260A B cell


122024AA431296Hs.139433ESTs 2.5


106657AW854339Hs.33476hypothetical protein 2.5
FLJ11937


126127N95428 gb:zb80d09.s1 Soares 2.5
senescent fibroblas


45 111836858394Hs.25119ESTs, Weakly similar 2.5
to YEXO_YEAST HYPOT


121470AA558958Hs.324751ESTs 2.5


120132W57554Hs.125019ESTs 2.5


107731AA016086Hs.2721ESTs, Weakly similar 2.5
O6 to 138022 hypotheli


118122AI186671Hs.48008ESTs 2.5


SD 106589AK000933Hs.28661Homo Sapiens cDNA FLJ100712.5
fis, clone HE


129948AI537162Hs.263988ESTs 2.5


115652BE093589Hs.38178hypothetical protein 2.5
FLJ23468


103076NM ribonucleotide reductase2.5
001D34 M2 polypeptide
Hs.75319


131019W28614Hs.306155chorionic somatomammotropin2.5
hormone 1 (p


100512D13317Hs.78915GA-binding protein transcription2.5
5 factor,


105393AF167570Hs.256583intedeukin enhancer 2.5
binding factor 3, 9


100571L14561Hs.78546ATPase, Ca++transporting,2.5
plasma membra


106890AA489245Hs.88500mitogen-activated protein2.5
kinase 8 tote


104276AW965275Hs.284288hqp0256 protein 2.5


()~113283T66813Hs.12947EST 2.5


118078N54321Hs.47790EST 2.5


120796A1247356Hs.96820ESTs 2.5


106265AA412176Hs.236463Homo Sapiens mRNA; cDNA2.5
DKFZp58610521 (f


102507052154Hs.193044potassium inwardly-rectifying2.5
channel, s


65 106508AI205785Hs.30348ESTs 2.5


104568AW629981Hs.172182poly(A)-binding protein,2.5
cytoplasmic 1


103698AA001021Hs.6685thyroid hormone receptor2.5
interactor 8


113947W84768 gb:zh53d03.s1 Soares 2.5
fetal liver-spleen-


132112AL021938Hs.40154jumonji (mouse) homolog2.5


70 129052BE275031Hs.158210hypothetical protein 2.4
MGC2555


117265AA451966Hs.43005RAB9-like protein 2.4


107834AA253162Hs.40838ESTs 2.4


113119T47910 gb:yb18b11.s1 Slratagene2.4
fetal spleen (9


133726AI803188Hs.252716oxysterol-binding protein-related2.4
protei


75 120548AA280356Hs.187634ESTs 2.4


121545AA412442Hs.98132ESTs 2.4


131136A8033099Hs.23413KIAA1273 protein 2.4


126589AW027809Hs.187698Homo Sapiens cytomegalovirus2.4
partial fus


115475A8033085Hs.40193hypothetical protein 2.4
KIAA1259


103760AA642973Hs.183842ubiquitin B 2.4


127889AI147408Hs.144941ESTs 2.4


124457AK000680Hs.266175phosphoprotein associated2.4
with GEMS


113721AF143885Hs.18190SST 2.4


g7


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
129079 Hs.108502hypothetical protein 2.4
AK000157 FLJ20150


123530 Hs.187772ESTs 2.4
AA608705


123592AAB05331Hs.112637ESTs 2.4


113474850752Hs.23856hypothetical protein 2.4
MGC5297


116728F13687Hs.227976EST 2~4


101759M80244Hs.184601solute carrier family 2.4
7 (cationic amino


131686NM Hs.30687GRB2-associated binding2.4
012296 protein 2


127841AW136558Hs.125246ESTs 2.4


102737851790Hs.239483Human clone 23933 mRNA2.4
sequence


l 129673D38552Hs.1191KIAA0073 protein 2.4
0


133095BE046490Hs.180677zinc finger protein 2.4
162


124540N63232 gb:yz39a12.s1 Morton 2.4
Fetal Cochlea Homo


113609T93263Hs.16B75ESTs, Weakly similar 2.4
to 523650 retrovir


128826240313Hs.106330Homo Sapiens clone 2.4
IMAGE:23371, mRNA
seq


15 129059AW069534Hs.279583CGI-81 protein 2.4


134092AA218558Hs.7905sorting nexin 9 2.4


132317BE262438Hs.44592beta-1,4 mannosyltransferase2.4


135278AA399542Hs.229671EST, Moderately similar2.4
to PEPTIDYL-PROL


128468T23625Hs.150580putative Uanslation 2.4
initiation factor


127407AW089514Hs.279681heterogeneous nuclear 2.4
ribonucleoprolein


132342AW162758Hs.45232ESTs, Weakly similar 2.4
1o ALU5_HUMAN ALU
5


113518AW367788Hs.323954postmeiotic segregation2.4
increased 2-lik


100330AW410976Hs.77152minichromosome maintenance2.4
deficient (S.


116046BE395293Hs.94491hypotheGcalprotein 2.4
FLJ20297


123910AA621262Hs.179923ESTs, Weakly similar 2.4
to S65657 alpha-1
G


101651AL037111Hs.75641galactose-1-phosphate 2.4
uridylyltransferas


100114X02308Hs.82962thymidylate synthetase2.4


125038AA812234Hs.270134hypothetical protein 2.4
FLJ20280


135191X16866Hs.301086cytochrome P450, subfamily2.4
IID (debrisoq


30 123258AA490929Hs.105274ESTs, Weakly similar 2.d
to RMS1 HUMAN REGUL


132380AW373665Hs.46853ESTs 2.4


114046BE018658Hs.141003Homo Sapiens cDNA: 2.3
FLJ21691 fis, clone
C


133582BE391579Hs.75087Fas-activated sednelthreonine2.3
kinase


134839D63479Hs.115907diacylglycerol kinase,2.3
delta (130kD)


3 105734AI952797Hs.10888hypothetical protein 2.3
S FLJ21709


101086AA382524Hs.250959histatin 1 2.3


118349N63786Hs.94149ESTs, Weakly similar 2.3
to ALU1 HUMAN ALU
S


101194L20971Hs.188phosphodiesterase 4B, 2.3
cAMP-specific (dun


130588AL030996Hs.16411hypothetical protein 2.3
LOC57187


101875BE241753Hs.74592special AT-rich sequence2.3
binding protein


118751N74210Hs.50454ESTs 2.3


125174W51835Hs.231082EST 2.3


105966AA142984Hs.5344adaptor-related protein2.3
complex 1, gamma


104624AA353125Ns.184721ESTs 2.3


45 131263AU077002Hs.24950regulator of G-protein2.3
signalling 5


105014AA121123Hs.269267ESTs, Weakly similar 2.3
to AF161361 1 HSPC


123423AA598484 gb:ae38f04.s1 Gessler 2.3
Wilms tumor Nomo s


128531H03721Hs.2953ribosomal protein Sl5a2.3


108876AI733860Hs.191453ESTs 2.3


130215BE301883Hs.152707glioblastomaamplifiedsequence2.3


132232AI522273Hs.42640ESTs 2.3


132664A1740461Hs.54542ESTs 2.3


105991AA215701Hs.186541ESTs, Weakly similar 2.3
to 138022 hypotheti


100253D38024Hs.157425double homeobox, 2 2.3


Jr 105574AA045281Ns.266175phosphoprotein associated2.3
with GEMS


100780BE561958Hs.302063immunoglobulin heavy 2.3
constant mu


134964AI803516Hs.272891hippocalcin-like protein2.3
4


132786BE083422Hs.56851hypothetical protein 2.3
MGC2668


104952AW076098Hs.74316desmoplakin (DPI, DPII)2.3


119127AA708035Hs.12248ESTs 2.3


104857A1920902Hs.19058ESTs, Moderately similar2.3
to 565657 alpha


107592AA694264Hs.60049ESTs 2.3


113378T80738Hs.14757ESTs 2.3


129226U40714Hs.239307tyrosyl-tRNA synthetase2.3


65 106898AA490069Hs.306676Homo Sapiens cDNA FLJ143022.3
fis, clone PL


130734AW137091Hs.18624KIAA1052 protein 2.3


125728AW954565Hs.57987B-cell CLLllymphoma 2.3
118 (zinc finger pro


113697T97183Hs.17992Homo Sapiens mRNA; 2.3
cDNA DKFZp434Ji726
(f


107104AU0766d0Hs.15243nucleolar protein 1 2.3
(120kD)


7~ 134267AI174596Hs.196209RAE1 (RNA export 1, 2.3
S.pombe) homolog


105777842755Hs.23096ESTs 2.3


115306AA280288Hs.88746ESTs 2.3


133363A1866286Hs.71962~ ESTs, Weakly similar2.3
to 836298 praline-r


129535AA397972Hs.169965chimerin (chimaerin) 2.3
1


75 121520AA412163Hs.164785ESTs 2.3


123808AA620552 gb:ae58g11.s1 Stratagene2.3
lung carcinoma


105700AW580830Hs.35254hypothetical protein 2.3
FLB6421


120820AA347417Hs.96869EST 2.3


128721AW403911Hs.266175phosphoprotein associated2.3
with GEMS


g0 107711W96141Hs.220687ESTs 2.3


102564U59423Hs.79067MAD (mothers against 2.3
decapentaplegic, Or


131868AW408296Hs.33532zinc finger protein 2.3
151 (pHZ-67)


122333AA625872Hs.98977ESTs, Moderately similar2.3
to T34561 hypot


$g


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
118865AA736405Hs.54530ESTs 2.3


128952AL043463Hs.6755RaP2 interacting protein2.3
8


133772BE379867Hs.76038isopentenyl-diphosphate2.3
delta isomerase


111795AI435437Hs.24567ESTs, Weakly similar 2.3
to KBF3 HUMAN NUCL


103437AV655598Hs.184211peptidase (mitochonddal2.3
processing) bet


123060AA482027Hs.142569ESTs, Weakly similar 2.3
to 138022 hypotheti


125466806234Hs.180461ESTs 2.3


100892BE245294Hs.180789S164 protein 2.3


121613AA416879Hs.193195ESTs, Weakly similar 2.3
to 2109260A B cell


1 133665AL036883Hs.75450delta sleep inducing 2.2
~ peptide, immunoreac


129248W04606Hs.171637hypothetical protein 2.2
MGC2628


126153H85692Hs.40730ESTs 2.2


125590823858Hs.143375Homo sapiens, clone 2.2
IMAGE:3840937, mRNA,


104960AA558677Hs.8928hypothetical protein 2.2
FLJ20291


1 113941AA531016Hs.22399hypotheGcalprotein 2.2
s FLJ14824


112540869751 gb:yi40a10.s1 Scares 2.2
placenta Nb2HP Homo


105322T87179Hs.16346ESTs, Weakly similar 2.2
to S57447 HPBRII-7


112003AW978731Hs.30i824hypothetical protein 2.2
PR01331


134733N87353Hs.89421CBFiinteracting coreprescor2.2


114620AA642974 gb:nr60h01.s1 NCI CGAP-Lym32.2
Homo sapiens


123451AI793211Hs.165372ESTs, Moderately similar2.2
to ALU1 HUMAN A


130850AB040922Hs.20237DKFZP566C134 protein 2.2


105561AA262881Hs.323836ESTs, Weakly similar 2.2
to altema6vely s


125957H41694 gb:yo06b06.r1 Scares 2.2
adult brain N2b5HB5


25 130362BE513050Hs.279681heterogeneous nuclearribonucleoprotein2.2


122682AA984531Hs.i59293ESTs 2.2


124250AA350256Hs.323875EST, Weakly similar 2.2
to 2109260A B cell


131392AA235153Hs.26320TRABID protein 2.2


128845AW503976Hs.10649basement membrane-induced2.2
gene


130453U80735Hs.173854PAX transcription activation2.2
domain tote


126973W46653Hs.251928nuclear pore complex 2.2
interacting protein


103156BE259039Hs.129953Ewing sarcoma breakpoint2.2
region 1


103163AU077018Hs.3235keratin 4 2.2


109252BE440157Hs.85944ESTs 2.2


35 131163AA099524Hs.23754ESTs 2.2


115292AA279956Hs.88672ESTs 2.2


122591A1188219Hs.99311ESTs, Weakly similar 2.2
to HSJ2-HUMAN DNAJ


124977F04819Hs.190452KIAA0365 gene product 2.2


103319X83492Hs.82359tumornecrosisfactorreceptorsupedami2.2


40 100370D79989Hs.184884KIAA0167 gene product 2.2


128992H04150Hs.107708ESTs 2.2


129928A1338993Hs.134535ESTs 2.2


108451AA079195 gb:zm92hi2.s1 Stratageneovariancancer2.2


133910AW835281Hs.77500ubiquitin specific 2.2
protease 4 (proto-one


45 106288A8037742Hs.24336KIAA1321 protein 2.2


134125NM-014781Hs.50421KIAA0203 gene product 2.2


101379X02994Hs.1217adenosine deaminase 2.2


112276853442Hs.26038ESTs, Weakly similar 2.2
to 138022 hypothet


106251Ri Hs.35101praline-rich Gla (G-carboxyglutamic2.2
2607 acid


50 125394BE178502Ns.173772ESTs, Weakly similar 2.2
to 178885 serinelth


103392X94563 gb:H.sapiens dbilacbp 2.2
gene exon 18 2.


112853T02843 gb:FB1 1H5 Fetal brain,2.2
Stratagene Homo s


133195AI434760Hs.279949KIAA1007 protein 2.2


135060AK001887Hs.259842protein kinase, AMP-activated,2.2
gamma 2 n


55 131381M92642Hs.26208collagen, type XVI, 2.2
alpha 1


134104L35253Hs.79107mitogen-activated protein2.2
kinase 14


105225AA211777 gb:zn57d02.s1 Stratagene2.2
muscle 937209 H


131320AA505691Hs.145696splicing factor (CC1.3)2.2


119419AI248013Hs.106532ESTs, Weakly similar 2.2
to 138588 reverse
t


103634BE541733Hs.180877H3 histone, family 2.2
3B (H3.38)


134624AF035119Hs.8700deleted in liver cancer2,2
1


126524245455Hs.182447heterogeneous nuclear 2.2
dbonucleoprotein


115556AL031778Hs.797nuclear transcription 2.2
factory, alpha


111898838944Hs.183475Homo sapiens clone 2.2
25061 mRNA sequence


65 100415D86970Hs.75822TGF81-induced anti-apoptotic2.2
factor 1


103898AA248884 gb:k3517.seq.F Human 2.2
fetal heart, Lambda


129501AI631811Hs.180403STRIN protein 2.2


127251AA936428Hs.128638ESTs 2.2


100613X52078Hs.101047transcription factor 2.2
3 (E2A immunoglobul


7~ 116332AA491208Hs.62620chromosome 6 open reading2.2
frame 1


128897AW979134Hs.10700hypothetical protein 2.2


111777AK001100Hs.41690desmocollin 3 2.2


128604AI879099Hs.102397GIOT-3 for gonadoiropin2.2
inducible transc


125585AW298113Hs.92909SON DNA binding protein2.2


75 129584AV656017Hs.184325CGI-76 protein 2.2


114461AA531187Hs.126705ESTs 2.2


121387AA405854 gb:zu66g08.s1 Scares 2.2
testis NHT Homo sap


109339AA3i4554Hs.27774ESTs, Highly similar 2.2
to AF1613491 HSPCO


129179AW969025Hs.109154ESTs 2.2


80 106711BE390125Ns.143187hypotheticalprotein 2.2


106424H61005Hs.37902ESTs 2.2


123949AA621665Hs.208957EST 2.2


127256A1738610Hs.267967ESTs, Moderately similar2.2
to ALUS_HUMAN


89


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
104868AF173867Hs.28906glucocorticoid modulatory2.2
element bindin


132984BE539199Hs.62112zinc finger protein 2.2
207


126383AB032977Hs.6298KIAA1151 protein 2.2


130557H51825Hs.268911ESTs, Weakly similar 2.2
to S65824 reverse


119232AI655226Hs.117659ESTs, Weakly similar 2.2
to T46481 hypotheti


105715BE621800Hs.29444putative small membrane2.2
protein NID67


124691805835Hs.110153ESTs 2.2


113649N94768Hs.16400ESTs, Weakly similar 2.2
to KIAA1435 protein


117040AW970600Hs.303261ESTs 2.2


1 128767M85169Hs.1050pleckstdn homology, 2.2
~ Sec7 and coiledlcoi


120602AA808018Hs.109302ESTs 2.2


107182A1311782Hs.20013GCIP-interacting protein2.2
p29


107357U63973Hs.103501rhodopsin kinase 2.2


125499H10543 gb:ym04c06.r1 Soares 2.1
infant brain 1 NIB
H


15126872AW450979 gb:Ul-H-BI3-ala-a-12-0.ULs12.1
NCI-CGAP_Su


113233T61955Hs.279867CGI-59 protein 2.1


128367AW611791Hs.150742ESTs 2.1


127432AW067708Hs.170311heterogeneous nuclear 2.1
ribonucleoprotein


114021AW235215Hs.16145ESTs 2.1


104455AL110261Hs.157211DKFZP586B0621 protein 2.1


134966AW402389Hs.920modulator recognition 2.1
factor 1


129765M86933Hs.1238amelogenin(Ychromosome)2.1


133461NM Hs.334345cytochrome P450, subfamily2.1
000762 IIA (phenobar


109639AA082650Hs.6217Homo Sapiens cDNA FLJ125212.1
fis, clone NT


25129794AF161399Hs.23259hypothetical protein 2.1
FLJi3433


134869AL157518Hs.90421PR02463 protein 2.1


110256H63947Hs.237955RAB7, member RAS oncogene2.1
family


128817BE395776Hs.168640ankylosis, progressive2.1
(mouse) homolog


120906NM Hs.97087CD3Z antigen, zeta 2.1
000734 polypeptide (TiT3
com


30134354M90391Hs.82127intedeukin 16 (lymphocyte2.1
chemoattracta


106048AW883367Hs.301732hypothetical protein 2.1
MGC5306


128352AW137413Hs.169942ESTs 2.1


115348AA281562Hs.292100ESTs 2.1


123474AA599209 gb:ag34b11.s1 Jia bone2.1
marrow stroma Hom


35107121A8015427Hs.250493zinc fingerprotein219 2.1


118509N22617Hs.43228Homo sapiens cDNA FLJ118352.1
fis, clone HE


135051AI272141Hs.83484SRY (sex determining 2.1
region Y)-box 4


109442AW296134Hs.86999ESTs, Weakly similarfo2.1
S65657 alpha-1G


126661AA009835Hs.269521ESTs 2.1


40129270AA357185Hs.109918ras homolog gene family,2.1
member H


125568AW615396Hs.105613ESTs 2.1


132867AF226667Hs.58553CTP synthase II 2.1


124656AW297702Hs.102915ESTs 2.1


128954AA346839Hs.209100DKFZP434C171 protein 2.1


45132985AL045579Hs.62113KIAA0717 protein 2.1


119247BE269047Hs.65234hypothetical protein 2.1
FLJ20596


106686N66397Hs.334825Homo Sapiens cDNA FLJ147522.1
fis, clone NT


131009AF169802Hs.22142cytochrome b5 reductase2.1
b58.2


112170BE246743Hs.288529hypothetical protein 2.1
FLJ22635


50130755BE293520Hs.18910prostate canceroverexpressedgenel2.1


117357N24829 gb:yx98h12.s1 Soares 2.1
melanocyte 2NbHM Ho


101613M24283Hs.168383intercellular adhesion2.1
molecule 1 (CD54)


127644N88858Hs.155101ATP synthase, H+transporting,2.1
mitochond


101183AA442324Hs.795H2A histone family, 2.
member 0 1


55100420D86983Hs.118893Melanoma associated 2.1
gene


129879AK001696Hs.13109Ran binding protein 2.1
11


122311NM Hs.i31915KIAA0863protein 2.1
014913


130566885474Hs.16073ESTs 2.1


113517A1874223Hs.293560ESTs 2,1


60115810AA426026Hs.187615ESTs 2.1


108743AI580150Hs.71074ESTs 2,1


129255AI961727Hs.109804H1histonefamily,memberX2.1


120766AA764879Hs.12570tubulin-specific chaperone2.1
d


126893AJ252060Hs.26320TRABID protein 2.1


65115254AA279024Hs.269316ESTs, Weakly similar 2.1
to S65657 alpha-1
C


105865BE279383Hs.26557plakophilin 3 2.1


120999AI972375Hs.29626hypothetical brain 2.1
protein my038


125636H12382Hs.25119ESTs, Weakly similar 2.1
to YEXO-YEAST HYPOT


117997N52090Hs.47420EST 2.1


70104333D82418Hs.29626hypothetical brain 2.1
protein my038


134315AA291183Hs.81648hypothetical protein 2.1
FLJ11021 similar 1o


135332AW393883Hs.98968hypothetical protein 2.1
FLJ23058


107279S57296Hs.323910v-erb-b2 avian erythroblastic2.1
leukemia


133097W03512Hs.6479hypothetical protein 2.1
MGC13272


75112563AW961220Hs.29282mitogen-activated protein2.1
kinase kinase


121782AW452957Hs.334698Homo Sapiens, clone 2.1
MGC:15203, mRNA, cam


111567F12628Hs.334786hypothetical protein 2.1
MGC16040


133912H42679Hs.77522major histocompatibility2.1
complex, class


134076AF086215 gb:Homo Sapiens full 2.1
length insertcDNA


g0116665F04405 gb:HSC2S8082 normalized2.1
infant brain cDN


133562M60721Hs.74870H2.0 (Drosophila)-like2.1
homeo box 1


129092D56365Hs.63525poly(rC)-binding protein2.1
2


106869AW975362Hs.292679ESTs 2.1




CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
130820 Hs.288798hypotheticalprotein 2.1
AL353934 FLJ21012


126277 Hs.15441Crm (Cramped Drosophila)-like2.1
AB037847


106392BE350058Hs.36787chromodomain helicase 2.1
DNA binding prolei


131902AA180145Hs.34348Homo sapiens mRNA; cDNA2.1
DKFZp434P0235 (f


120734AA299948 gb:ESTi 2544 Uterus 2.1
tumor I Homo Sapiens


113070AB032977Hs.6298KIAA1151 protein 2.1


116031AA452239Hs.103329KIAA0970 protein 2.1


123869AA620924Hs.112923EST 2.1


106145AA424791Hs.5734meningioma expressed 2.1
anfigen 5 (hyaluron


1 109061AA160896 gb:zo79c07.s1 Stratagene2.1
0 pancreas(93720


126348T16243Hs.6473Homo Sapiens cDNA FLJ139922.1
fis, clone Y7


133231AK000517Hs.6844hypotheticalprotein 2.1
FLJ20510


123132A1061582Hs.324179Homo Sapiens cDNA FLJ123712.1
fis, clone MA


117452N34687Hs.44054otoein (GSK38 interacting2.1
protein)


1 128538844214Hs.101189ESTs 2.1



111945840663Hs.12494dESTs 2.1


119155861715Hs.310598ESTs,ModeratelysimilartoALU12.1
HUMAN


124362AL046406Hs.103483KIAA1798 protein 2.1


129198N57532Hs.109315KIAA1415 protein 2.1


122059AA431737Hs.98749EST, Moderately similar2.1
to T42671 hypoth


115643AA404276Hs.123253hypothetical protein 2.0
FLJ22009


112558AK001621Hs.15921hypotheficalprotein 2.0
FLJ10759


115355AA262292Hs.88445ESTs 2.0


130724AK001507Hs.306084Homo Sapiens clone FLB69142.0
PR01821 mRNA,


25 125360AW898892Hs.189741ESTs 2.0


104926BE298808Hs.33363DKFZP434N093 protein 2.0


119468A1911535Hs.6657hypothetical protein 2.0
bK1048E9.5


132891BE267143Hs.59271U2(RNU2) small nuclear 2.0
RNA auxiliary fac


100237D30715Hs.306333Human PAP (pancreafitis-associated2.0
prot


30 105335AW291165Hs.25447ESTs 2.0


106727AA357001Hs.34045hypothetical protein 2.0
FLJ20764


126053H64450 gb:yu62d01.r1 Weizmann 2.0
Olfactory Epithet


115084BE383668Hs.42484hypothetical protein 2.0
FLJ 10618


128408AI183407Hs.143704EST 2.0


35 132311AI765559Hs.20072myosin regulatory light2.0
chain interactin


113626T94318Hs.17359ESTs, Moderately similar2.0
to RL44 HUMAN 6


116379AA448588Hs.71252hypotheticalprotein 2.0
DKFZp761C169


105474AL134843Hs.219614f-box and leucine-rich 2.0
repeat protein 11


108922AA115268Hs.269263ESTs 2.0


123720AA609734Hs.112755EST 2.0


128902AA036637Hs.107052ESTs 2.0


113226A1821008Hs.10697ESTs 2.0


106798BE252749Hs.20558hypothetical protein 2.0
FLJ20345


106665BE090009Hs.323164hypothetical protein 2.0
MGC2217


105952AI767152Hs.lBiESTs, Weakly similar 2.0
400 to 178885 serinelth


127248AA364195 gb:EST75015 Pineal gland2.0
7l Homo Sapiens


112972AI684745Hs.165983hypothefical C2H2 zinc 2.0
finger protein FL


128148AA918175Hs.126637ESTs 2.0


116176AA311152Hs.288708hypothetical protein 2.0'
FLJ21562


126457AA007489Hs.50382ESTs 2.0


112610AW500106Hs.23643serinelthreonine protein2.0
kinase MASK


109249AA194730Hs.268189hypothetical protein 2.0
FLJ20436


121292AA401807 gb:zv65f11.s1 Soares-total_fetus-Nb2HF8-2.0


128605AW058113Hs.102402Mad4 homolog 2~0


55 127705AJ003322 gb:AJ003322 Selected 2.0
chromosome 21 cDNA


134674AF219139Hs.87726KIAA0154 protein; ADP-ribosylalion2.0
facto


107529BE515065Hs.296585nucleolar protein (KKEID2.0
repeat)


116411AA608897Hs.321618hypothetical protein 2.0
FLJ12525


111576T88827Hs.15489ESTs 2.0


127002AL353940Hs.24979hypotheficalprotein 2.0
DKFZp761P1010


112662885436Hs.268814ESTs 2.0


126250AL050391Hs.321247Homo sapiens mRNA; cDNA2.0
DKFZp586A181 (fr


101045J05614 gb:Human proliferating 2.0
cell nuclear anfi


117186H98988Hs.42612ESTs, Weakly similar 2.0
to ALU1 HUMAN ALU S


6S 122110AI123000Hs.301240melanocortin 1 receptor2.0
(alpha melanocyt


119849A1074585Hs.58440ESTs 2.0


124395N29963Hs.272095ESTs, Weakly similar 2.0
to 138022 hypotheti


131600NM 7 carnitine palmitoyltransferase2.0
00437Hs.29331I, muscle


112774895770Hs.35455ESTs 2.0


7~ 109751AB033492Hs.6679hHDC for homolog of 2.0
Drosophila headcase


102377U40343Hs.29656cyclin-dependent kinase2.0
inhibitor 2D (p1


115197818656Hs.6749ESTs 2.0


102808BE242818Hs.179606nuclear RNA helicase, 2.0
DECD variant of DE


128869AA768242Hs.80618hypothetical protein 2.0


75 111229AW389845 ESTs 2.0
Hs.110855


129330AL079310Hs.92260high-mobility group 2.0
protein 2-like 1


105448NM_001186 BTB and CNC homology 2.0
Hs.154276 1, basic leucine z1


127391AW380893 hypothetical protein 2.0
Hs.11039 MGC2722


102337AI814663Hs.170133forkhead box 01A (rhabdomyosarcoma)2.0


g0 121897AA427419Hs.229162EST, Weakly similar 2.0
to ZN91 HUMAN ZINC


107902AA02fi627Hs.61358ESTs 2.0


129340H75334Hs.11050F-box only protein 9 2.0


101097BE245301Hs.89414chemokine (C-X-C motif),2.0
receptor 4 (fus


91


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
124864AW970168Hs.185706ESTs 2.0


118485AA508515Hs.291049ESTs 2.0


116715AL117440Hs.170263tumor protein p53-binding2.0
protein,1


130743AL049266Hs.18724Homo Sapiens mRNA; 2.0
cDNA DKFZp564F093
(fr


118677AW971146Hs.293187ESTs 2.0


100020 2.0


123252AW968776Hs.287586Homo Sapiens cDNA FLJ136482.0
fis, clone PL


134977AL044963Hs.306121leukocyte receptor 2.0
cluster (LRG) encoded


115334AA702972Hs.65300ESTs 2.0
'


111790AW769683Hs.6734ESTs, Weakly similar 2.0
to S26650 DNA-bindi


129101NM Hs.108665zinedin 2.0
013403


132676N925B9Hs.261038ESTs, Weakly similar 2.0
to 138022 hypothet


111018AI287912Hs.3628mitogen-acfivated protein2.0
kinase kinase


105933AF078544Hs.194686solute tamer family 2.0
25 (mitochonddal


1 110679AA004798Hs.108311ESTs, Weakly similar 2.0
s to T00351 hypolhefi


120861AA350394Hs.96952ESTs . 2.0


132430AW973652Hs.283105ESTs 2.0


115026AA251972Hs.188718ESTs 2.0


128660AA011597Hs.177398ESTs 2.0


2~ 134554A1184316Hs.85273relinoblastoma-binding2.0
protein 6


109592AI198059Ns.26370ESTs 2.0


123636AA609263 gb:af13cO8.s1 Scares 2.0
tesfis NHT Homo sap


132610AA160511Hs.5326amino acid system N 2.0
transporter 2; porcu


122652AA454641 gb:zx99d05.s1 Soaves-NhHMPu_S12.0
Homosapi


25 120467AW292562Hs.187628ESTs 2.0


126046AA804957Hs.119840ESTs 2.0


128179AW293689Hs.127116ESTs 2.0


123349A8033042Hs.29679cofactor roquired far 2.0
Sp1 transcriptions


106208AK001674Hs.22630cofactor required for 2.0
Sp1 transcriptions


125832AA628600Hs.117587ESTs 2.0


133317AC005258Hs.70830U6 snRNA-associated 2.0
Sm-like protein LSm7


132886AW978168Hs.5912F-box only protein 2.0
7


127447AA386192Hs.193482Homo Sapiens cDNA FLJ119032.0
fis, clone HE


133149AA370045Hs.6607AXINi up-regulated 2.0


35 120468AW967675Hs.96487ESTs, Highly similar 2.0
to S08228 ribosomal


106487AI697340Hs.135265Homo Sapiens clone 2.0
FLB8436 PR02277 mRNA,


126770A1292320Hs.81361heterogeneous nucleardbonucleoprotein2.0


120592AA830664Hs.i43974ESTs 2.0


100944L07518Hs.159593mucin 6, gastric 2.0


40 101887AW967413Hs.83958transducin-like enhancer2.0
of split 4, hom


125324807785 gb:yf15c06.ri Soaresfetalliverspleen2.0


133906BE386038Hs.77492heterogeneous nuclear 2.0
ribonucleoprotein


113408NM Hs.115945mannosidase, beta A, 2.0
005908 lysosomal


115613AW136951Hs.173946hypothetical protein 2.0
FLJ10486


45 107468AA740979Hs.91389ESTs 2.0


100554M95923 gb:Human 12-lipoxygenase2.0
mRNA, partial c


120476NM Hs.104305death effectorfilament-forming2.0
014922 Ced-4-li


117160AA322302Hs.183302PCTAIRE protein kinase2.0
2


115582AW245047Hs.136164cutaneous T-cell lymphoma-associated2.0
to


125536F08266Hs.77948ESTs,WeaklysimilartoALU12.0
F1UMANALUS


100842U05597 gb:Human anion exchanger2.0
3 cardiac isofo


133207AI561173Hs.67688ESTs 2.0


122053AI637498Hs.98745ESTs 2.0


121080AA617830Hs.28310ESTs 2.0


55 113316T70318Hs.268581ESTs 2.0


113137AW952129Hs.293225ESTs, Weakly similar 1.9
to FLDED-1 [H.sapie


100416AW505086Hs.196914minor histocompatibility1.9
anfigen HA-1


133975C18356Hs.295944tissue factor pathway 1.9
inhibitor 2


103872AI816078Hs.21756translafion factor 1.9
suit homolog


132439AK001942Hs.4863hypothetical protein 1.9
DKFZp566A1524


126082H81188Hs.269571ESTs 1.9


124677801073 gb:ye84c03.s1 Scares 1.9
fetal liver spleen


123385BE149685Hs.17767KIAA1554 protein 1.9


103138X65965 gb:H.sapiens SOD-2 1.9
gene for manganese
su


65 104867AA278898Hs.225979hypothetical protein 1.9
similar to small G


128668AI754363Hs.103422Homo Sapiens cDNA FLJ146301.9
fis, clone NT


125826M20681Hs.7594solute tamer family 1.9
2 (facilitated glu


113701T97301Hs.18026ESTs 1.9


134447M58603Hs.83428nuclear factor of kappa1.9
light polypeptid


70 128895AW467000Hs.106985ESTs 1.9


112719AI200957Hs.19301Homo sapiens, Similar 1.9
to Nedd-4-like ubi


102552NM tumor protein p53-binding1.9
005426 protein, 2
Hs.44585


131186270200Hs.246112KIAA0788 protein 1.9


133347BE257758Hs.71475acid cluster protein 1.9
33


75 133388AW245631Hs.182447heterogeneous nuclearribonucleoprotein1.9


112266AI652534Hs.25934ESTs, Weakly similar 1.9
to HSHU11 histone
H


100336N76101Hs.8127KIAA0144 gene product 1.9


113479A1023133Hs.10739ESTs 1.9


135231BE613615Hs.74280hypothetical protein 1.9
FLJ22237


go 123783AA610112 gb:af19g05.s1 Soares_total-Fetus_Nb2HF8-1.9


113016NM KIAA0414 protein 1.9
014007
Hs.127649


132761AI815537Hs.323502nuclear RNA export 1.9
factor 1


128536AW955065Hs.101150Homo Sapiens, clone 1.9
IMAGE:4054156, mRNA,


92


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
126663AW518478Hs.181297ESTs 1.9


103973AA305729Hs.18272amino acid transporter1.9
system A1


106742AW591428Hs.27556hypothetical protein 1.9
FLJ22405


129793AW207000Hs.126857Homo sapiens cDNA FLJ129361.9
fis, clone NT


105888AW970672Hs.9247protein kinase, AMP-activated,1.9
alpha 1 c


101892AI825838Hs.75206protein phosphatase 1.9
3 (formerly 2B), cat


125511AJ271379Hs.76194dlwsomal protein 55 1.9


126751AI378328Hs.77256enhancer of zeste (Drosophila)1.9
homolog 2


129111AL080155Hs.226372DKFZP434J154 protein 1.9


1 128750T80270Hs.104788hypothetical protein 1.9
~ LOC55565


133531BE276738Hs.74578DEADIH (Asp-Glu-Ala-AspIHis)1.9
box polypep


125704855094Hs.26239Human DNA sequence 1.9
from clone RP11-43882


100157D14661Hs.119Wilms'tumour 1-associaUng1.9
protein


125845AK001440Hs.131840hypothetical protein 1.9
FLJ10578


I 134682AW882645Hs.88044sprouty (Drosophila) 1.9
S homolog 1 (antagoni


106565NM Hs.227602KIAA1116 protein 1.9
014892


106706AB037810Hs.18760KIAA1389 protein 1.9


125761868351 gb:yh99b03.r1 Soares 1.9
placenta Nb2HP Homo


116470AI272141Hs.83484SRY (sex determining 1.9
region Y)-box d


123264AI681270Hs.99824BCE-1 protein 1.9


126096F08208Hs.283844similar to rat tdcarboxylate1.9
tamer-li


104995AK001690Hs.16390hypotheticalprotein 1.9
FLJ10035


133424AA350994Hs.20281KIAA1700 1.9


132450AA100012Hs.48827hypothetical protein 1.9
FLJ12085


25131803073737Hs.284289vitiligo-associated 1.9
protein VIT-1


116548D20433 gb:HUMGS0i407 Human 1.9
promyelocyte Homo
so


113815AA386192Hs.193482Homo Sapiens cDNA FLJ119031.9
fis, clone HE


100245AL039248Hs.3094KIAA0063 gene product 1.9


113677270200Hs.246112KIAA0788 protein 1.9


3~134470X54942Hs.83758CDC28 protein kinase 1.9
2


134937AI251449Hs.171939ESTs 1.9


134506AW247364Hs.84285ubiquitin-conjugating 1.9
enzyme E21 (homolo


126469BE384361Hs.182885ESTs, Weakly similar 1.9
to JC5024 UDP-galac


115261AA938293Hs.60088hypothetical protein 1.9
MGC11314


35125198W69474Hs.323140ESTs 1.9


115317AA303799Hs.300141ribosomal protein L39 1.9


112342AW410273Hs.92614longevity assurance 1.9
(LAGt, S. cerevisiae


117329AA524065Hs.93670Homo Sapiens cDNA: 1.9
FLJ22664 fis, clone
H


116353AB032966Hs.131728KIAA1140 protein 1.9


114459AW445217Hs.103362ESTs 1.9


133903X63692Hs.77462DNA (cytosine-5-)-methyltransferase1.9
1


116083AA455706Hs.44581heat shock protein 1.9
hsp70-related protein


130037AI498631Hs.111334femtin,lightpolypeptide1.9


102273BE391815Hs.75981ubiquitin specific 1.9
protease 14 (tRNA-gua


45120452AL022328Hs.104335hypothetical protein 1.9
IMAGE3510317


116432BE271922Hs.71243ESTs, Weakly similar 1.9
to zinc finger prot


115916A1052731Hs.91910ESTs 1.9


120827AA382525Hs.132967Human EST clone 1228871.9
mariner transposo


129602AI282193Hs.198298v-src avian sarooma 1.9
(Schmidt-Ruppin A-2)


105693BE250951Hs.181368U5 snRNP-specific protein1.9
(220 kD), orlh


102316034301 gb:Human nonmuscle 1.9
myosin heavy chain
II


131422AW607731Hs.26670Human PAC clone RP3-515N11.9
from 22q11.2-q


128434AI190914Hs.143880ESTs 1.9


1170116AA581602Hs.41840ESTs 1.9


55102006AL048967Hs.172207non-POU-domain-containing,1.9
octamer-bindi


121335AA404418 gb:zw37e02.s1 Soares_total_fetus_Nb2HF8_1.9


105905AA401533Hs.19440ESTs 1.9


125165W45350 gb:zc81 h08.s1 Pancreatic1.9
Islet Homo sapi


109875H03260Hs.30385ESTs 1.9


109152AW380723Hs.73451ESTs, Weakly similar 1.9
to S55024 nebulin,


126203AK001035Hs.130881B-cell CLLllymphoma 1.9
11A (zinc finger pro


122530AW959741Hs.40368adaptor-related protein1.9
complex 1, sigma


124506BE273688Hs.182447heterogeneous nuclearribonucleoprotein1.9


130525AA361850Hs.322149Human clone 137308 1.9
mRNA, partial cds


65127226AL036559Hs.3463ribosomal protein S23 1.9


106465AA971576Hs.225951topoisomerase-rotated 1.9
function protein 4


106970AA52i366Hs.24252ESTs 1.9


134275A1878910Hs.3688cisplatin resistance-associated1.9
overexpr


126825AA100230 gb:z181c01.s1 Stratagene1.9
colon (937204)


7~132443AW246148Hs.268371hypothetical protein 1.8
FLJ20274


104631AA002064Hs.18920ESTs 1.8


111468H62647Hs.205481ESTs 1.8


114317AA524839Hs.469succinate dehydrogenase1.8
complex, subunit


126158N55989Hs.16390hypothetical protein 1.8
FLJ10035


75113782AK001567Hs.311002Homo Sapiens cDNA FLJ107051.8
fis, clone NT


119229T03229 gb:FB5C2 Fetal brain, 1.8
Slratagene Homo so


105930AF016371Hs.9880peptidyl prolyl isomerase1.8
H (cyclophilin


127245AA323958 gb:EST26810 Cerebellum1.8
II Homo Sapiens c


100967BE011845Hs.251064high-mobility group 1.8
(nonhistone chromoso


105149BE089288Hs.8958Homo Sapiens cDNA FLJ 1.8
12024 fis, clone HE


104542829657 gb:F1-1179D 22 week 1.8
old human fetal live


124236AF086006 gb:Homo Sapiens full 1.8
length insertcDNA


127155AA284993 gb:zt23e10.r1 Soares 1.8
ovary tumor NbHOT
H


93


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
126854AJ275986Hs.71414transcription factor 1.8
(SMIF gene)


107021AK001342Hs.14570hypothetical protein 1.8
FLJ22530


110023AW294701Hs.31040ESTs 1.8


114899AK000342Hs.77646Homo sapiens mRNA; cDNA1.8
DKFZp761 M0223 (f


127315AFi gb;Homo sapiens clone 1.8
16622 FLBd217 mRNA segue


110384H45282Hs.268798ESTs 1,8


132693BE244200Hs.55075KIAA0410 gene product 1.8


127684AA668631Hs.32556KIAA0379 protein 1.8


127297AW629485Hs.140720GSK-3 binding protein 1.8
FRAT2


1 104249AF004231Hs.22405leukocyte immunoglobulin-like1.8
~ receptor,


112652BE269699Hs.235782solute carrier family 1.8
21 (organic anion


110312BE256986Hs.1i896hypotheticalprotein 1.8
FLJ12089


100417NM Hs.78054pro-mRNA splicing factor1.8
014003 similar to S. c


120532AA262354Hs.i86648ESTs, Weakly similar 1.8
to 138022 hypotheti


I 127629AA293279Hs.29173hypothetical protein 1.8
S FLJ20515


100739M69287Hs.2083CDGlike kinase 1 1.8


110636H72868Hs.19110ESTs 1.8


132957BE244044Hs.61469hypothetical protein 1.8


115467AI366784Hs.48820TATA box binding protein1.8
(TBP)-associate


20 132161W31634Hs.180799hypotheticalprotein 1.8
FLJ22561


129510AW968504Hs.123073CDC2-related protein 1.8
kinase 7


126805F32658Hs.101359chromosome 6 open reading1.8
frame 32


129295063127Hs.110121SEC7 homolog 1.8


127823AW972893Hs.78869transcription elongation1.8
factor A (S11),


25 10459DAW373062Hs.83623nuclear receptor subfamily1.8
1, group I, m


111959840978Hs.271498ESTs,ModeratelysimilartoALU1_HUMANA1.8


109303AA199857Hs.269291ESTs 1.8


112501AA972447Hs.288833Nomo sapiens mRNA; cDNA1.8
DKFZp434K087 (fr


127303AA366951 gb:EST77963 Pancreas 1.8
tumor III Homo sapi


115982W92113 gb:zh48e01.r1 Soares 1.8
fetal liver-spleen-


123331AA497013 gb:ae32g02.s1 Gessler 1.8
Wilms tumor Homo s


111598811505Hs.268912ESTs 1.8


121643AA640987Hs.193767ESTs 1.8


105012AF098158Hs.9329chromosome 20 open reading1.8
frame 1


35 118761AW7991D9Hs.226755ESTs 1.8


128765AF073310Hs.143648insulin receptor substrate1.8
2


118103AA4D1733Hs.184134ESTs 1.8


134595NM Hs.29282mitogen-activated protein1.8
002401 kinase kinase


134212AA654353Hs.17779EBP50-PDZ interactor 1
of 64 kD 8


40 128033AI248705Hs.149321ESTs .
1.8


126972NM Hs.95260Autosomal Highly Conserved1.8
016255 Protein


111122N63753Hs.16492DKFZP564G2D22 protein 1.8


114798AA159181Hs.54900serologically defined 1.8
colon cancer antig


106349AW954310Hs.127270KIAA1545 protein 1.8


45 135358BE622827Hs.99486hypothetical protein 1.8
FLJ13044


116223AF045458Hs.47061unc-51 (C. elegans)-like1.8
kinase 1


116654226324Hs.79204ESTs, Weakly similar t.8
to 138022 hypolheti


124554N65961 gb:za27d03.s1 Soaresfetalliverspleen1.8


120259AW014786Hs.192742hypothetical protein 1.8
FLJ 12785


123044AK001035Hs.130881B-cell CLLllymphoma 1.8
11A (zinc finger pro


125261W90351Hs.110134ESTs, Highly similar 1.8
to CREB-binding pro


135026N92165Hs.93231ESTs 1.8


129951AL110282Hs.268024Nomo Sapiens, clone 1.8
IMAGE:3873720, mRNA


125768AI557486Hs.119122ribosomal protein Ll3a 1.6


55 114122846128Hs.12751ESTs 1.8


133047AA310600Hs.63657peptide:N-glycanase 1.8
similar to yeast PNG


133589L37368Hs.75104RNA-binding protein i.8
Si, sedne-rich doma


130872061084Hs.226307phorbolin (similar to 1.8
apolipoprotein B m


1334988E299587Hs.85301calcium binding protein1.8
P22


131144AA305255Hs.23528HSPC038 protein 1.8


104261AW24836dHs.5409RNA polymerase I subunil1.8


115507A1083668Hs.50601hypothetical protein 1.8
MGC10986


109073T05003Hs.10056hypotheticalprotein 1.8
FLJ14621


115363AA214618Hs.152759activator of S phase 1.8
kinase


65 112657AW844878Hs.19769hypothetical protein 1.8
MGC4174


102960AI904738Hs.76053DEADIH (Asp-Glu-Ala-AspIHis)1.8
box polypep


125549820215 gb:yg18b09.r1 Soares 1.8
infant brain 1N18 H


133797AL133921Hs.76272retinoblastoma-binding 1.8
protein 2


125048AW440068Hs.59425hypothetical protein 1
FLJ23323 8


103403X95406 gb:H.sapiens cyclin ,
E gene. 1,8


123546AA608817Hs.112597EST 1.8


124694806108 gb:ye94h05.s1 Soaresfetalliverspleen1.8


102406043177 (NONE) 1,g


130695T97205Hs.17998ESTs, Weakly similar 8
to 2109260A B cell 1


75 123951A8012922Hs.173043metastasis-associated .
1-like 1 1.8


118533N71861Hs.49413ESTs 1_g


123197AA489250 gb:aa57h12.s1 NCI CGAP_6CB11.8
Homosapiens


125656AW516428Hs.78687neutral sphingomyelinase1.8
(N-SMase) activ


100154H60720Hs.81892KIAA0101 gene product 1
8


106876N52821Hs.269412ESTs, Moderately similar_
to ALU7_HUMAN A 1.8


128339AL121087Hs.296406KIAA0685 gene product 1,8


105939AL137728Hs.12258Homo Sapiens mRNA; cDNA1.8
DKFZpd34B0920 (f


102495NM_006762Hs.79356Lysosomal-associated 1.8
multispanning membr


94


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
100221028383 gb:Human mRNA for ATP 1.8
synthase B chain,


101741NM Hs.326198transcription factor 1.8
003199 4


101701NM-002436Hs.i861membrane protein, palmitoylated1.8
1 (55k0)


107119AI375499Hs.27379ESTs 1.8


Jr 134362U47742Hs.82210zinc finger protein 1.8
220


127964F06298 gb:HSC13F081 normalized1.8
infant brain cDN


101437M20681Hs.7594solute carver family 1.8
2 (facilitated glu


106204AA188734Hs.21479ubinuclein 1 1.8


112716AW590680Hs.110802von Willebrand factor 1.8


109779AB029396Hs.3353beta-1,3~lucuronyltransferase1.8
1 (glucur


111369AA535740Hs.170263tumor protein p53-binding1.8
protein,1


135204AF067515Hs.183418cell division cycle 1.8
2-like 1 (PITSLRE
pr


105788AB009698Hs.23965solute carver family 1.8
22 (organic anion


110997AW862823Hs.168052KIAA042i protein i.8


I 111620814853Hs.307478EST, Weakly similar 1.8
S to 139058 hypotheti


115618H11695Hs.322901disrupter of silencing1.8
10


115904AI167560Hs.61297ESTs 1.8


107510BE613332Hs.132055ESTs, Weakly similar 1.8
to GNMSLL reUoviru


116435AAi86761Hs.334812hypothetical protein 1.8
DKFZp586K0717


112399860920Hs.296770KIAA1719 protein 1.8


127426AA854756Hs.124076ESTs 1.8


125175W52355Hs.303030EST 1.8


132972AAD34365Hs.288924Homo Sapiens cDNA FLJ113921.8
tis, clone HE


125982898091 gb:yr30e11.r1 Soares 1.8
fetal liver spleen


115620AA399997Hs.211610CUG triplet repeat, 1.8
RNA-binding protein


128115AI435590Hs.130168ESTs 1.8


106880AI493206Hs.32425ESTs 1.7


101199L22075Hs.1666guanine nucleotide 1.7
binding protein (G
pr


104159BE386983Hs.283685hypothetical protein 1.7
FLJ20396


30 101368M13058Hs.73952praline-rich protein 1.7
Haelll subfamily 2


103646AW248439Hs.2340junction plakoglobin 1.7


130717AA334274Ns.i8368DKFZP56480769 protein 1.7


124981N25485Hs.330310maternal G10 Uanscript1.7


124770AA984414Hs.120429ESTs 1.7


35 126926AA179472Hs.832ESTs, Highly similar 1.7
to A41029 integrin


101636BE392781Hs.89474ADP-ribosylation factor1.7
6


123553AI494291Hs.111977ESTs 1.7


127172AA292208Hs.251278KIAA1201 protein 1.7


130621AW513087Hs.16803LUC7 (S. cerevisiae)-like1.7


116925H73110Hs.260603ESTs, Moderately similar1.7
to A47582 B-ce


108845AW362901Hs.68864ESTs, Weakly similar 1.7
fo phosphalidylseri


128092AA904617Hs.166229ESTs 1.7


128193AJ224442Hs.155020putative methylUansferase1.7


113965AI268666Hs.19631ESTs, Weakly similar 1.7
to 138022 hypotheti


45 106620052562Hs.296317KIAA1789 protein 1.7


102926W28363Hs.239752nuclear receptor subfamily1.7
2, group F, m


114964BE085271Hs.8834~ng finger protein 1.7
3


101800NM-006433Hs.105806granulysin 1.7


130094NM_001471Hs.167017gamma-aminobutyric 1.7
acid (GABA) B recepto


120112AA180240Hs.6083Homo Sapiens cDNA: 1.7
FlJ21028 fis, clone
C


109978H09356Hs.22528ESTs 1.7


121252AA393907Hs.97179ESTs 1.7


127768AW085002Hs.156187ESTs 1.7


125445AI452722Hs.7709WW domain binding protein1.7
1


55 100052 1.7


119863AA081218Hs.58608Homo Sapiens cDNA FLJ142061.7
fis, clone NT


134333AW888411Hs.81915leukemia-associated 1.7
phosphoprotein p18
(


123541AW976511Hs.112592ESTs 1.7


134191W26632Hs.7979KIAA0736 gene product 1.7


103305X82279 gb:H.sapiens Fas, Apo-t1.7
gene (promoter a


112411843090Hs.271510ESTs, Moderately similar1.7
to ALU1 HUMAN A


100598AL121734Hs.146409cell division cycle 1.7
42 (GTP-binding prot


113610T93279 gb:ye25f01.s1 Stratagene1.7
lung (937210) H


105593AA279341Hs.174151aldehyde oxidase 1 1.7


65 125317299348Hs.i ESTs, Weakly similar 1.7
12461 to 138022 hypotheti


125956AK000214Hs.129014hypothetical protein 1.7
FLJ20207


105105861532Hs.87016hypothetical protein 1.7
FLJ22938


132791AB029551Hs.7910RlNG1 and YY1 binding 1.7
protein


116996H83935Hs.40535ESTs 1.7


133335BE251012Hs.263812nuclear distribution 1.7
gene C (A.nidulans)


120959BE247692Hs.102469putative nuclear protein1.7


105621AL040058Hs.6375uncharacterized hypothalamus1.7
protein HTO


106181AI803651Hs.191608ESTs 1.7


125661AA491830Hs.25689ESTs 1.7


75 127585AA604144Hs.190632ESTs 1.7


112035AI955289Hs.300759ribosomal protein L36 1.7


102870M64437Hs.234799breakpoint cluster 1.7
region


108039AA280319Hs.288840PR01575 protein 1.7


125898AK001823Hs.92287Homo Sapiens mRNA; 1.7
cDNA DKFZp564C2478
(f


114740N70103 gb:za53e10.s1 Soaresfetal1.7
liver spleen


120304AA192469Hs.271838ESTs 1.7


103433X98001Hs.78948Rab geranylgeranyltransferase,1.7
beta subu


116180AA463902Hs.13522ESTs, Weakly similar 1.7
to 138022 hypothet




CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
105269AF174499Hs.6764histone deacetylase 1.7
6


125431AW851639Hs.75584polymyositislsclerodertna1.7
autoantigen 2 (


133579X75346Hs.75074mitogen-activated protein1.7
kinase-activat


105355AL031447Hs.26938Homo Sapiens, clone 1.7
IMAGE:4053044, mRNA,


129601AB032964Hs.i15726KIAA1138protein 1.7


113739AA356599Hs.173904ESTs 1.7


100840U04816Hs.183418cell division cycle 1.7
2-like 1 (PITSLRE pr


122878AA847744Hs.99640ESTs 1.7


119495BE144608Hs.55533ESTs 1.7


1 125669851308Hs.333256ESTs, Weakly similar 1.7
O to ALUB-HUMAN ALU


109891H04757Hs.323176ESTs 1.7


126884U49436Hs.286236KIAA1856 protein 1.7


132977AA093322Hs.301404RNA binding motif protein1.7
3


101396BE267931Hs.78996proliferating cell nuclear1.7
antigen


I 104730AW139789Hs.16370Homo Sapiens cDNA FLJ116521.7
S fis, clone HE


102205BE242291Hs.197540hypoxia-inducible factor1.7
1, alpha subuni


112945AW138458Hs.20787Homo Sapiens cDNA: FLJ216861.7
fis, clone C


129902AA076278Hs.13277hypotheticalprotein 1.7
FLJ22054


107157AW853745Hs.286035hypothetical protein 1.7
FLJ22686


ZO 133229AL737480Hs.6834KIAA10i4protein 1.7


129912AF155096Hs.107213hypothetical protein 1.7
FLJ20585


119811AW137640Hs.231444Homo sapiens, Similar 1.7
to hypothetical pr


126323N77584Hs.68644Homo Sapiens microsomal1.7
signal peptidase


133134AF198620Hs.65648RNA binding motif protein1.7
8A


115278AK002163Hs.301724hypothetical protein 1.7
FLJ11301


133817AW578716Hs.7644H1 histone family, member1.7
2


130753AA205223Hs.189phosphodiesterase 4C, 1.7
CAMP-specific (dun


107463AW952022Hs.315164hypothetical protein 1.7
similar to actin re


121009NM-001533Hs.2730heterogeneous nuclear 1.7
obonucleoprotein


3O 125546H09950 gb:ym01d12.r1 Soares 1.7
infant brain 1N18 H


129991828386Hs.179925ESTs, Weakly similar 1.7
to ALUB HUMAN ALU


119015N95490Hs.29700hypotheticalprotein 1.7
FLJ20094


100058 1.7


116655AF271732Hs.68090bodging integrator-3 1.7


3 119898893325Hs.58690ESTs 1.7



105021H07960Hs.306044CGI-OS protein 1.7


102098N25485Hs.330310maternal G10 transcript1.7


126730AA442429 gb:zv70g02.r1 Soares 1.7
total-fetus-Nb2HF8-


113427T85105Hs.15471ESTs 1.7


122317T85253Hs.290874ESTs, Weakly similar 1.7
to ALUB_HUMAN ALU S


130503BE208491Hs.295112KIAA0618 gene product 1.7


117348N24157 gb:yx96b12.s1 5oares 1.7
melanocyte 2NbHM Ho


127033AF769301Hs.9098sulfate transporter 1.7
1


128554AW972147Hs.101395hypothetical protein 1.7
MGC11352


45 124733820547Hs.100830ESTs 1.7


106310898185Hs.17240ESTs 1.7


122638AL137476Hs.123609Homo Sapiens mRNA; cDNA1.7
DKFZp43410623 (f


101075L03532Hs.79024heterogeneous nuclear 1.7
ribonucleoprotein


126659T16245 gb:NIB1005R Normalized 1.7
infant brain, Ben


127717F12209Hs.173380CK2 interacting protein1.7
1; H00024c prote


105441N28522Hs.8935quinolinate phosphoobosyltransferase1.7
(n


104188AA478423Hs.300870Homo sapiens mRNA; cDNA1.7
DKFZp547M072 (fr


134750L29073Hs.1139cold shock domain protein1.7
A


106826BE253927Hs.24983hypothetical protein 1.7
from EUROIMAGE 2021


55 113511T89578Hs.189740ESTs 1.7


111070NM Hs.171834PCTAIRE protein kinase 1.7
006201 1


129091AA056483Hs.301463Human Chromosome 16 1.7
BAC clone CIT987SK-A


129710AJ277841Hs.120963ELG protein 1.7


132833U78525Hs.57783eukaryotic translation 1.7
initiation factor


125775AW514585Hs.29205alpha integon binding 1.7
protein 63


113675T81034Hs.14841ESTs 1.7


100487AU076640Hs.15243nucleolar protein 1 1.7
(120kD)


119302T25725 gb:ESTDIR152CD34+DIRECTIONALHomosapie1.7


128245AA993101Hs.170486ESTs 1.7


65 130322NM Hs.154545PDZ domain containing 1.7
014247 guanine nucleotide


135363AW589601Hs.119Wilms' tumour 1-associating1.7
protein


125181840815Hs.12396ESTs, Weakly similar 1.7
to 2004399A chromos


132347BE271016Hs.169850ESTs, Weakly similar 1.7
to T21554 hypotheti


127206AW816490Hs.337508ESTs 1.7


7~ 121880AW946155Hs.7750hypothetical protein 1.7
AL133206


125797H03117Hs.111497similar to mouse neuronal1.7
protein 15.6


114601AA075566 gb:zm88f06.s1 Stratagene1.7
ovarian cancer


126278AA417302Hs.63042DKFZp564J157 protein 1.7


120964AA398085Hs.142390ESTs 1.7


75 133634AL035071Hs.234279microtubule-associated 1.7
protein, RPIEB fa


107025AA825523Hs.21255ESTs, Weakly similar 1.7
to 138022 hypotheti


105638AA493453Hs.247817H2B histonefamily, memberA1.7


135398M16029Hs.287270ret proto-oncogene (multiple1.7
endocone


115794AA424900Hs.112227membrane-associated 1.7
nucleic acid binding


102063T35901Hs.75117interleukin enhancer 1.7
binding factor 2, 4


100188AW247090Hs.57101minichromosome maintenance1.7
deficient (S.


130868AB037855Hs.171917hypotheticalprotein 1.7
FLJ11085


110493A1247707Hs.36915ESTs 1.7


96


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
115041AA252457Hs.86543ESTs, Moderately similar
to T00256 hypot 1.7


128764AW024282Hs.104938hypothetical protein MGC15906
1.7


134065X78992Hs.78909butyrate responsefactor2(EGF-response
1.7


101082BE616731Hs.80645interferon regulatory factor
1 1.7


130945020582Hs.2i49acfin like protein 1.7


106974AI817130Hs.9195Homo Sapiens cDNA FLJ13698
fis, clone PL 1.7


126752A1073373Hs.326923EST, Weakly similar to 138022
hypothetic 1.7


133327AL390127Hs.7104Kruppel-like factor 13 1.7


127005T81309Hs.251664insulin-like growth factor
2 (somatomedi 1.7


1 105615AA281959Hs.5210glia maturation factor, gamma
~ 1.7


116295AA742596Hs.91216ESTs, Weakly similar to 2004399A
chromos 1.7


111587AI125867Hs.20734ESTs 1.7


104570AW978870Hs.131828ESTs 1.7


134752BE246762Hs.89499arachidonate 5-lipoxygenase
1.7


I 130430W27893Hs.150580putative Uanslalion inifiafion
S factor 1.7


119244AW407564Hs.275865ribosomal protein S18 1.7


131152NM Hs.23598CREB binding protein (Rubinstein-Taybi
004380 s 1.7


133419BE242676Hs.73172growlhfactorindependentl
1.7


106542AA339541Hs.24956hypothetical protein FLJ22056
1.7


20 116482AW207000Hs.126857Homo Sapiens cDNA FLJ12936
fis, clone NT 1.7


132555AW500131Hs.171763CD22 anfigen 1.7


125840A8028986Hs.12064ubiquifin specific protease
22 1.7


115416AA283893Hs.337079ESTs 1.7


120041AA830882Hs.59368ESTs 1.7


126295A1281459Hs.270114ESTs 1.7


122528AA449804Hs.292154stromal cell protein 1.7


Table 28:
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
Pkey CAT number Accession
108451 13766 27 AA079195 AA084955 AA126308 AA084956
3 5 124236 46919 1 AF086006 H64722 H65212 H66282
115982 173_2 W92113 AA702794 BE044316 W91984 AA679375 T94184 AA679335 BE503t26
AW502118 BE467367 AA584550 AW139964 893353
AW088477 AI887846 AW502624 W81697 W81696 AA447817 AA447667 F13631 AW268271
AA055366 AW629027 AA677404 AA831618
AI124782 AA889402 AA765804 AA765530 AA055698 AA594019 AI267368 AA456946 893354
AF264624 AW668618 AA601493
116665 1394292 1 F04405 BE173130
125165 1852047 1 W45350 W45406
125324 1692163 1 807785 T85948 T86972
126053 1601238 1 H64450 H64464
125499 1562851~1 H10543 811878
126127 1205826 1 N95428 W24040 AW751366 H81987
45 125546 356478 1 H09950 818413 AA570553 AW973425
125549 1702179 1 820215 818767
125761 1744008 1 868351 868364
127155 200358 1 AA284993 AA478122 AA477923
125957 1583542 1 H41694 H45213
125982 1766315 1 898091 W92898
127245 226662 1 AA323958 AA370268
127248 227560 1 AA364195 AA325029 AW962050
127262 231725 1 AA828125 AA834883 AA330555
126659 1541209 1 T16245 819694 F13545 H10299 T66048 T65279 H18006
5 127303 258778 1 AA366951 AAd70999 AA469425
127315 37938 1 AF116622 AI 1 14507 AA640834 AA377999
126730 297653 1 AA442429 T19477
103898 187213 3 AA248884
126872 142696_1 AW450979 AA136653 AA136656 AW419381 AA984358 AA492073 BE168945
AA809054 AW238038 BE011212 BE011359 BE011367
(7~ BE011368 BE011362 BE011215 BE0i1365 BE011363
112540 1605263 1 869751 870467 H69771 H80879 H80878
127705 966283 2 AJ003322 AJ003324
121335 279548 1 AA404418 A1217248
120734 208882 1 AA299948 AA299949
65 114620 32062_8 AA642974 AA084223
122652 26401 30 AA454641
123636 genbank-AA609263 AA609263
100842 tigr_HT4398 005597
116548 genbanILD20433 D20433
7~ 123783 genbanILAA610112 AA610112
125032 genbank T74884 T74884
123808 genbanILAA620552 AA620552
102316 entrez_U34301 034301
102406 entrez 043177 043177
75 134076 40321-1 AF066215 W02702 AA284288 W25655
104542 829657
113119 genbank T47910 T47910
104799 genbank_AA029703 AA029703
127964 135151 1 F06298 818057
120809 genbank-AA346495 AA346495
113610 genbank_T93279 T93279
113947 genbanILW84768
101045 enUez J05614
97


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
129969genbank
N57818


117031genbank-H88353


101447enUez
M2i305


124540genbank-N63232


124554genbank-N65961


117348genbank_N24157


117357genbank
N24829


124677genbank_R01073


124694genbanILR06108


1 103138entrez_X65965
~


103305entrez
X82279


103392entrez_X94563


103403entrez_X95406


119229genbank
T03229


1 119302_
genbank-T2572S


126825430458 AA100230
1 AA100274


105225genbank_AA211777


121292genbank_AA401807


112853genbank-T02843T02843


20 121387genbank_AA405854


114601genbank-AA075566


100221entrez_D28383D28383


123197genbanILAA489250AA489250


114740379876 N70103 N70020
1 AW383189
AI207469
W00935
W00906
AA551569
AI343637
AA135199


25 123331genbank-AA497013


107794genbanILAA019255


100554figr-HT2241M95923


123423genbank_AA598484


123474genbank
AA599209


3 109061-
0 genbank-AA160896


TABLE Leukemia (ALL) Compared
3A: to Normal Adult Hematopoiefic
About Tissues
1346
Genes
Up-regulated
in
Acute
Lymphocytic


Table leukemia (ALL) compared were selected
3A to normal adult hematopoieticfrom 35403
lists tissues. These probesets on
about
1346
genes
up-regulated
in
acute
lymphocytic


35 the array such
AffymetrixlEos that the
Hu01 ratio of
GeneChip "average'
leukemia
to "average"
normal
adult hematopoietic
tissues
was greater
than or
equal to
3Ø The
"average"


leukemia
level
was
set
to
the
65"'
percentile
amongst
various
ALL
samples.
The
"average"
normal
adult
hematopoietic
tissue
level
was
set
to
the
75'"
percentile
amongst
various
non-


malignant order to background levels of non-specificamongst the
hematopoietic remove hybridization, the 10'" tissues was
tissues. gene-specificperoenUle value subtracted
In from


both numerator ated.
the and the
denominator
before
the ratio
was evacu


Pkey:Unique
Eos probesel
identifier
number


ExAccn:Exemplar
Accession
number,
Genbank
accession
number


UnigenelD: Unigene
number


UnigeneTitle: title
Unigene
gene


R1: Rafio
of leukemia
to hematopoietic
tissues


45 Pkey ExAccn UnigenelD UnigeneTitle R1


129498AA449789 Hs.75511 connective tissue growth 57.88
factor


100458S74019 Hs.247979 pre-B lymphocyte gene 1 49.45


133774X54079 Hs.76067 heat shock 27kD protein 48.42
1


102564U59423 Hs.79067 MAD (mothers against decapentaplegic,41.49
Dr


So 130650AB040951 Hs.284208 DKFZP434N161 protein 35.88


132922AF249745 Hs.6066 Rho guanine nucleofide 35.74
exchangefactor


112254AA852097 Hs.25829 ras-related protein 33.26


106706AB037810 Hs.18760 KIAA1389 protein 32.39


101050AU077324 Hs.1832 neuropeptide Y 30.68


55 102455U48705 Hs.75562 discoidin domain receptor 26.81
family, member


101838BE243845 Hs.75511 connective tissue growth 25.46
factor


113374T79925 Hs.269i65 ESTs, Weakly similar to 24.69
ALU1 HUMAN ALU S


134125NM_014781Hs.50421 KIAA0203 gene product 24.63


106943AW888222 Hs.9973 tensin 23.14


130069AI754813 Hs.146428 collagen, type V, alpha 23.06
1


119073BE245360 Hs.279477 ESTs 22.53


130444M12125 Hs.300772 tropomyosin 2(beta) 21.96


100420D86983 Hs.118893 Melanoma associated gene 21.05


114324AF084481 Hs.26077 Wolfram syndrome 1 (wolframin)18.95


65 101400M15990 Hs.i94148 v-yes-1 Yamaguchi sarcoma 18.46
viral oncogene


102759NM 005100Hs.788 A kise (PRKA) anchor protein17.88
(gravin)


100893BE245294 Hs.180789 Si64 protein 16.75


131689A8012124 Hs.30696 transcription factor-like 16.60
5 (basic helix


106410AB037787 Hs.26229 neuroligin 2 16.51


101304AA001021 Hs.6685 thyroid hormone receptor 15.60
interactor 8


131524A8040927 Hs.301804 KIAA1494 protein lS.Ot


107794AA019255 gb:ze56e10.s1 Soares yeti 14.78
N2b4HR Homo


129213Ai146494 Hs.109525 ESTs, Weakly similar to 14.76
IRX2 HUMAN IROQU


116068AA328041 Hs.194329 hypothetical protein FLJ2117414.24


75 134416X68264 Hs.211579 melanoma cell adhesion 14.06
molecule


134545AI902899 Hs.85155 butyrate response factor 14.03
1 (EGF-response


114009AI248544 Hs.103000 KIAA0831 protein 13.93


115110AK001671 Hs.11387 KIAA1453 protein 13.75


130107AF112977 Ns.172887 phytanoyl-CoA hydroxylase 13.60
(Refsum diseas


8~ 133558X66945 Hs.748 fibroblast growth factor 13.60
receptor 1 (fms


100871T85231 Hs.179661 tubulin, beta 5 13.50


101462AL035668 Hs.73853 bone morphogenetic protein13.48
2


120809AA346495 gb:EST52657 Fetal heart 13.33
II Homo sapiens


98


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
123340AA504264 Hs.i82937 peptidytprotytisomeraseA(cyclophitin13.25


103460A1021993 Hs.14331 S100 calcium-binding 13.25
protein A13


102460048959 Hs.211582 myosin, light polypeptide13.14
kise


100168H73444 Hs.394 adrenomedullin 13
09


115844AI373062 Hs.332938 hypothetical protein .
MGC5370 13.00


130103Y13492 Hs.14909B smoothelin 12.92


(02407AW602154 Hs.82143 E74-like factor 2 (ets 12.03
domain transcript


113632T94907 Hs.188572 ESTs 11.85


118951NM 000448Hs.7395B recombition activating 11.73
gene 1


100305NM-004941Hs.171872 DEADIH (Asp-Glu-Ala-AspIHis)11.63
box polypep


109737AA055415 Hs.13233 ESTs, Moderately similar11.55
to A47582 B-cel


122577AA829725 Hs.334437 hypothetical protein 11.49
MGC4248


115147AA745781 Hs.38399 hypothetical protein 11.40
MGC2454


132303BE177330 Hs.325093 Homo sapiens cD: FLJ2121011.37
fis
clone C


I 103176AL021154 Hs.76884 , 11.17
5 inhibitor of D binding
3, domint neg


108358M81933 Hs.1634 cell division cycle 11.15
25A


104584AA704538 Hs.i93777 ESTs 11.12


106777AF037261 Hs.33787 vinexin beta (SH3-containing11.08
adapter mot


121054AW976570 Hs.97387 ESTs 10
90


119400T92767 gb:ye27dO6.s1 Stratagene.
lung (937210) H 10.83


126610AI911353 Hs.191391 ESTs 10.83


134555034879 Hs.85279 hydroxysteroid (17-beta)10.80
dehydrogese 1


131555T47364 Hs.278613 interferon, alpha-inducible10.79
protein 27


130979NM-012446Hs.169833 single-stranded-D-binding10.70
protein


~Jr113783AL359588 Hs.7041 hypothetical protein 10.65
DKFZp762B226


123503AW975051 Hs.293156 ESTs, Weakly similar 10.60
to 178885 serine/th


117031H88353 gb:yw21a02.s1 Morton 10.45
Feiai Cochlea Homo


100752T81309 Hs.251664 insulin-like growth 10.44
factor 2 (somatomedi


102618AL037672 Hs.81071 extracellular maUix 10.36
protein 1


30 113089T40707 Hs.270862 ESTs 10.33


132089W22007 Hs.39122 hypothetical protein 10.29
MGC15737


101663NM-003528Hs.2178 H2B histone family, 10.23
member 0


104876AI933f28 Ns.25220 tike-glycosyttransferase10.23


106370AF039B43 Hs.18676 sprouty (Drosophila) 10
homolog 2 18


3 129406A8018255 Hs.111138 KIAA0712 gene product .
5 10.18


115354AA281636 Hs.334827 ESTs 10.13


123077AA485229 Hs.105649 ESTs 10.05


131273AW206008 Hs.283378 Homo Sapiens cD: FLJ217789.95
fis, clone H


126177AW752782 Hs.129750 hypothetical protein 9.83
FLJ10546


133699BE501689 Hs.75617 collagen, type IV, alpha9.80
2


110855AB007928 Hs.28169 KIAA0459 protein 9.65


111826835975 gb:yh91b07.s1 Soares 9.58
placenta Nb2HP Homo


126947240778 Hs.191837 ESTs 9.50


116674AI768015 Hs.92127 ESTs 9
48


45 129087AI348027 Hs.108557 hypothetical protein .
PP1057 9.46


114837BE244930 Hs.166895 ESTs 9.45


120009A1080491 Hs.93270 ESTs, Moderately similar9.45
to S65657 alpha


112483AW969785 Hs.285885 Homo Sapiens cD FLJ113219.40
fis, clone PL


103487AA743603 Hs.172108 nucleoparin 88kD 30
9


105675AL390083 Hs.271277 hypothetical protein .
from EUROIMAGE 3636 9.28


129158NM 004413Hs.109 dipeptidase 1 (rel) 9.23


114394T34462 Hs.103291 neuritin 9,17


133331Y1d487 Hs.738 ritwsomal protein L14 9.11


114787AA156509 Hs.231892 ESTs, Weakly similar 9
to S65657 alpha-1 G 10


55 125502AW977181 Hs.194718 zinc finger protein .
265 9.03


132325N37065 Hs.44856 hypothetical protein 9.01
FLJ12116


127968AA83020f Hs.i24347 ESTs 9.00


114605AL157423 Hs.306478 Homo Sapiens m8; cD 8.93
DKFZp76100511 (f


114875AA235609 Hs.236443 Homo Sapiens m8; cD 8
DKFZp564N1063 (f 93


129898A1672731 Hs.13256 ESTs .
8.89


106263W21493 Hs.28329 hypothetical protein 8.89
FLJ14005


117130AA748850 Hs.125830 bladdercanceroverexpressed8.88
protein


105553AA256756 Hs.31178 ESTs 8.85


103657273677 gb:H.sapiens gene encoding8.83
plakophilin 1


105831AA329449 Hs.247302 twisted gastrulation 8.82


106375AW872878 Hs.289072 hypothetical protein 8.80
FLJ22175


114518AW163267 Hs.106469 suppresser of vari (S.cerevisiae)8.75
3-like


123433AW450922 Hs.112478 ESTs 8.67


134558NM 001773Hs.85289 CD34 antigen 67
8


115893AI652127 Hs.d8419 ESTs .
8.67


128621AA032197 Hs.102558 Homo Sapiens, clone 8.60
MGC:5352, m8, comp


122798AW366286 Hs.145696 splicing factor (CC1.3)8.58


112554871489 Hs.29196 EST 8.55


129969N57818 gb:yv59d07.s1 Soaresfetalliverspleen8.53


75 131558AA453208 Hs.28726 RAB9, member RAS oncogene8.45
family


134027297630 Hs.226117 Ht hisione family, member8.45
0


134138AB023169 Hs.7935 KIAA0952 protein 8.43


120030A1076355 Hs.58694 ESTs 6.43


101005NM 005239Hs.85146 v-ets avian erythroblastosis8.33
virus E26 0


115423AI499516 Hs.89303 ESTs 8.33


104946AW242407 Hs.73848 caroinoembryonic an&gen-related8.30
cell ad


131965W79283 Hs.35962 ESTs 8.30


126426AA125984 gb:zn27h06.r1 Slratagene8.28
neuroepithelium


99


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
108886AW248434 Hs.91521 hypothetical protein 8,26


107985T40064 Hs.71968 Homo sapiens m8; cD DKFZp564F0538.25
(fr


114239AL137667 Hs.267445Homo sapiens m8; cD DKFZpd34B2318.23
(fr


124281AI333756 Hs.111801arsete resistance protein8.23
11 ARS2


7099 H93699 gb:yvt6a11.s1Soaresfetalliverspleen8.20


119432AL120247 Hs.40109 KIAA0872 protein 8,15


115967A1745379 Hs.42911 ESTs 8,15


132355D87942 Hs.46328 fucosylUansferase 2 (secrotor8.13
status in


108339AW151340 Hs.51615 ESTs, Weakly similar to 8.10
ALU7_HUMAN ALU S


131694NM_0002d6Hs.3076 MHCclass II fransactivator8.05


104897N33937 Hs.10336 ESTs 8.03


120266A1807264 Hs.205442ESTs, Weakly similar to 8.03
T34036 hypotheti


130404A1672727 Hs.76753 endoglin (Osier-Rendu-Webersyndrome8.00
1)


115729AA417812 Hs.38775 ESTs 8.00
127
16


2 A1798703 Hs.143702ESTs, Weakly similar to 7.95
S70029 probable


131693AW963776 Hs.110796SARI protein 7,83


113107AI821027 Hs.8429 ESTs 7,8D


122282BE246331 Hs.98401 Homo sapiens m8 full lengfh7.90
inserf cDN


111040AI435502 Hs.14931 ESTs 7,80
2


1 A1022103 Hs.12d511ESTs 7,8p
7987


125317299348 Hs.112461ESTs, Weakly similar to 7,88
138022 hypoiheti


105242AI564857 Hs.27888 ESTs, Weakly similar to 7.75
serinefthreonine


t00421D86985 Hs.79276 KIAA0232 gene product 7,71


114359NM 016929Hs.283021chloddeinfracellularchannel57.70
119


772 AJ250839 Hs.582d1 gene for serinelthreonine7.70
protein lose


124040023752 Hs.32964 SRY (sex determining region7.65
Y)-box 1 t


134361BE549343 Hs.82208 acyf-Coenzyme A dehydrogese,7.57
very long


105476AL117352 Hs.i20828Human D sequence from 7.55
clone RP5-876810


113289T66900 Hs.188446ESTs 7.50
122


707 NM 002039Hs.239706GRB2-associated binding 7.50
protein 1


130055AI566248 Ns.146355v-abl Abelson murine leukemia7.49
viral onco


108766AF145713 Hs.61490 schwannomin-interacting 7.45
protein 1


107957236842 Hs.57548 ESTs 7.45


123116AW190412 Hs.183738FERM, RhoGEF (ARHGEF) 7.38
3J~123190 and pleckstrin dom


AA489212 Ns.105228EST 7.38


129574AA026815 Hs.i 1463UMP-CMP kise 7.38


115274C01566 Hs.86671 ESTs 7.35


102571060115 Hs.239069four and a half LIM domains7,34
1


116845AA649530 gb:ns44f05.s1 NCI CGAP_Alvi7.33
Homosapiens


134851AB011124 Hs.90232 KIAA0552 gene product 7.33


1D1780M82882 Hs.154365E74-like factor 1 (ets 7.28
domain franscript


125042T78906 Hs.269432ESTs, Moderately similar 7.28
to ALU1 HUMAN A


118472AL157545 Hs.42179 bromodomain and PHD finger7.25
containing, 3


108700AA121518 Hs. t EBTs, Moderately similar 7.23
109 9354D to 2109260A 8 0


411 898881 Hs.109655sex comb on midleg (Drosophila)-like7.20
1


127692A10219t2 Hs.187983EBTs 7.18


128501AL133572 Hs.199009protein containing CXXC 7.18
domain 2


107727AA149707 Hs.173091ubiquitin-like 3 7,14


118D89AI762507 Hs.d7878 ESTs 7,12



106025AV653785 Hs.173334ELL-RELATED R POLYMERASE 7.10
II, ELONGATIO


1221 AW593206 Hs.98785 Ksp37 protein 7.08
t
1


119674W60379 Hs.57773 EBTs 7.05


126607W87425 Hs.114688ESTs 7.05


121545AA4124d2 Hs.98132 ESTs 7.05
113


287 T66847 Hs.194040ESTs, Weakly similar to 7.03
138022 hypotheti


126672AA255592 Hs.203631EBTs, Weakly similar to 7.00
altertively sp


132087H14d86 Hs.3903 Cdc42 effector protein 6,87
4; binder of Rho


118697N22706 Hs.43234 EBTs 8,g7


100295M74782 Hs.172689interleukin 3 receptor, 6.95
101 alpha (low affin


188 L20320 Hs.184298cyclin-dependent kise 6.95
7 (homolog of Xe


121481AA41193i gb:zu03g05.s1 Soares_testis-NHT6.95
Homo sap


113003AW292315 Hs.7215 ESTs 6.93


101851BE260964 Hs.82045 midkine (neurile growth-promoting6.91
factor


113529AI190741 Ns.t77415Finkel-Biskis-Reillymurinesarcomaviru6.90
132


887 AA195831 Hs.273385guanine nucleotide binding6.90
protein (G pr


113560T91015 Hs.268626ESTs 6.85


123440A1733692 Hs.112488ESTs 6.83


130390AAd90770 Hs.182382ESTs 6.83


133889048959 Hs.211582myosin, light polypeptide6.83
kise


113573889379 Hs.15990 ESTs 6.80


112453863899 Hs.28455 ESTs 8,7g


125221AA236115 Ns.120785ESTs 6.78


134081AL034349 Hs.79005 protein tyrosine phosphatase,6.77
receptor f


127610AA960867 Hs.150271ESTs, Highly similar fo 8.75
1 unmed protein


05486AW449258 Hs.6187 ESTs 6,75


107796AA058848 Hs.60797 ESTs 8,71


132754A1752244 Hs.75309 eukaryolic translation 6.71
elongation factor


105806AF206019 Hs.110347REVi (yeasthomolog)-like 6.70


110837H03109 Hs.108920HT018 protein 6.65
g0


117698N62293 Hs.45107 ESTs 6.65


128994AF205849 Hs.107740Kruppel-like factor 2 6.65
(lung)


129131AB026436 Hs.177534dual specificity phosphatase6.65
10


108528AA650558 Hs.325202ESTs, Highly similar to 6.62
GRAS-HUMAN GUANI


100


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131009AF169802Hs.22142 cytochrome b5reductase 6.61
b58.2


129389NM 012445Hs.288126 spondin 2, extracellular6.60
matrix protein


125278AI218439Hs.129998 enhancerofpolycomb 1 6.59


124667W24320 Hs.102941 Homo Sapiens cD: FLJ215316.59
fis, clone C


105640AA001021Hs.6685 thyroid hormone receptor6.58
inieractor 8


106474BE383668Hs.42484 hypothefical protein 6.58
FLJ10618


105808AI133161Hs.286131 CGI-101 protein 6.53


120087AF186780Hs.79219 RaIGDS-like gene; KIAA09596.52
protein


100514AU076887Hs.28491 spermidinelspermine N1-acetyllransferase6.50


108378A1368460Hs.74615 platelet-derived growth 6.50
factor receptor,


133350AI499220Hs.71573 hypothefical protein 6.50
FLJ10074


115673AA406341Hs.269908 Homo Sapiens cD FLJ119916.48
fis, clone HE


133410Y07847 Hs.73088 RAS-related on chromsome6.48
22


131281AA251716Hs.25227 ESTs 6.46


105510242047 Hs.283978 Homo Sapiens PR02751 6.45
m8, complete cds


128766AW160432Hs.296460 craniofacial development6.45
protein 1


114530AA601038Hs.191797 ESTs, Weakly similar 6.43
to S65657 alpha-1 G


120120BE547267Hs.59791 hypothetical protein 6.40
MGC13183


120593AA748355Hs.193522 ESTs 6.40


125832AA628600Hs.117587 ESTs 6.38


129637NM 004606Hs.1179 TATA box binding protein6.38
(TBP)-associate


115302AL109719Hs.47578 ESTs 6.33


126137AA312594Hs.99115 hypothetical protein 6.30
FLJ20689


114465BE621056Hs.131731 hypothetical protein 6.29
FLJ11099


125562AI494372Hs.98968 hypotheficalprotein FLJ230586.29


127380AF070554Hs.15535 Homo Sapiens clone 245826.26
m8 sequence


106956806428 Hs.226351 ESTs 6.25


105962AW880358Hs.339808 hypothetical protein 6.25
FLJ10120


109416BE268388Hs.86945 ESTs, Weakly similar . 6.23
to A46010 X-linked


3 111116AK002039Hs.26243 Homo Sapiens cD FLJ111776.23
0 fis, clone PL


127282AA347158Hs.185780 ESTs 6.23


113074AK001335Hs.31137 proteintyrosine phosphatase,receptort6.21


101664AA436989Hs.121017 H2Ahistonefamily,memberA6.20


103317X83441 Hs.166091 IigaselV, D,ATP-dependent6.20


133894AW021236Hs.180433 rTS beta protein 6.19


109260AW978515Hs.131915 KIAA0863 protein 6.18


112772AI992283Hs.35437 ESTs, Moderately similar6.18
to 138026 MLN 6


132050AI267615Hs.38022 ESTs 6.18


113009723699 Hs.7246 ESTs 6.17


118835AA535246Hs.50852 ESTs 6.16


125626A1038854Hs.180789 S164 protein 6.15


117086AA581602Hs.41840 ESTs 6.14


101960AL036287Hs.194662 calponin 3, acidic 6.13


104488N56191 Hs.106511 protocadhedn 17 6.13


127695AA714731Hs.291457 ESTs, Weakly similar 6.13
to heterogeneous r1


127894AL121053Hs.5534 Homo Sapiens cD FLJ129616.13
fis, clone NT


113595792056 Hs.290240 ESTs, Moderately similar6.10
to ALU2_HUMAN A


120784AW752101Hs.16580 hypothetical protein 6.10
FLJ11026


115004AA329340Hs.4867 mannosyl (alpha-1,3-)-glycoprotein6.08
beta-


129740BE165866Hs.83623 nuclear receptor subfamily6.05
1, group I, m


117483N72185 Hs.44189 ESTs 6.04


103815BE245294Hs.180789 S164 protein 6.03


122040AA847758Hs.111030 ESTs 6.03


109638AW977747Hs.119120 E3 ubiquifin ligase SMURFt6.02


SS 112727791029 Hs.15069 ESTs 6.01


120273AA176688Hs.269284 ESTs 6.00


122127AW207175Hs.106771 ESTs 6.00


126046AA804957Hs.119840 ESTs 5.99


119774A8032977Hs.6298 KIAA1151 protein 5.98


106265AA412176Hs.236463 Homo Sapiens m8; cD DKFZp586105215.98
(f


111987NM 015310Hs.6763 KIAA0942 protein 5.98


123619AA602964 gb:no97c02.s1 NCI-CGAP_Pr25.96
Homo Sapiens


128122AI267491Hs.160593 ESTs 5.95


128473778277 Hs.100293 0-linked N-acetylglucosamine5.95
(Glcc) tr


102283AWi61552Hs.83381 guanine nucleotide binding5.94
protein 11


122468AA448172Hs.137687 ESTs, Highly similar 5.93
to K6B1 HUMAN RIBOS


101801M86407 Hs.1216 actinin, alpha 3 5.93


107059BE614410Hs.23044 RAD51 (S. cerevisiae) 5.92
homolog (E colt Re


108908AA136569Hs.10848 KIAA0187 gene product 5.90


121470AA558958Hs.324751 ESTs 5.90


131938AF176085Hs.34956 neural polypyrimidine 5.89
tract binding prot


109613H47315 Hs.27519 ESTs 5.89


109384AA219172Hs.86849 ESTs 5.88


118559N68456 Hs.49519 ESTs 5.88


102010002687 Hs.385 fms-related tyrosine 5.86
kise 3


105921AA421973Hs.169119 ESTs, Weakly similar 5.85
to 725731 hypotheti


124298H91679 gb:yv04a07.s1 Soares 5.85
fetal liver spleen


120827AA382525Hs.132967 Human EST clone 122887 5.84
mariner transposo


103331AI825463Hs.147996 protein kise, X-linked 5.82


g0 135052AL136653Hs.93675 decidual protein induced5.80
by progesterone


115219AA262776Hs.269314 Homo Sapiens cD FLJ141235.78
fis, done MA


121899855341 Hs.50421 KIAA0203 gene product 5.78


135217AA453880Hs.9658 hypothetical protein 5.77
FLJ11790


101


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123973C14805 gb:C14805 Clontech human5.77
aorta polyA+mR


112605879374 Hs.29852 ESTs 5.76


110151H18835 Hs.31608 hypothetical protein 5.75
FLJ20041


129889AA810932 Hs.131899 ESTs, Weakly similar 5.75
to T00370 hypotheti


102638U67319 Hs.9216 caspase 7, apoplosis-related5.73
cysteine pr


121501AA470687 Hs.104772 ESTs 5.73


124921893082 Hs.332635 ESTs 5.70


109850AI150548 Hs.23155 ESTs 5.70


120594AW136478 Hs.509d ring finger protein 5.70
10


1 126433AA325606 gb:EST28707 Cerebellum 5.70
~ II Homo Sapiens c


100455AW888941 Hs.75789 N-mycdownstreamregulated5.69


106565NM_014892Hs.227602 KIAAi116protein 5.68


120912AA376690 Hs.167650 ESTs 5.68


127209AA305023 Hs.81964 SEC24 (S. cerevisiae) 5.68
related gene Tamil


I 107606AF207989 Hs.330425 Homo Sapiens, Similar 5.67
S to G protein-coupl


106597A1091277 Hs.302634 fizzled (Drosophila) 5.66
homolog 8


102126AW950870 Hs.78961 protein phosphatase 5.65
1, regulatory (inhib


100064 AFFXcontrol-TrpnX-3 5.63


108758AA127395 Hs.222414 ESTs 5.63


20 101392NM 002507Hs.1827 nerve growth factor 5.61
receptor (TNFR super


102211BE314524 Hs.78776 putative transmembrane 5.60
protein


107427W26975 Hs.46736 hypothetical protein 5.60
FLJ23476


135175M91463 Hs.95958 solute carrier family 5.60
2 (facilitated glu


111764A1420368 Hs.290259 ESTs, Weakly similar 5.58
to 138022 hypotheti


25 119405793865 Hs.91085 ESTs 5.58


126464A1990046 Hs.54780 transcription tertnition5.58
factor, R po


133865AB011155 Hs.170290 discs, large (Drosophila)5.50
homolog 5


123255AA830335 Hs.105273 ESTs 5.57


122861AA335721 Hs.119394 ESTs 5.56


112046AA383343 Hs.22116 CDC14 (cell division 5.55
cycle 14, S. cerevi


132906BE613337 Hs.234896 geminin 5.55


109001A1056548 Hs.72116 hypothetical protein 5.55
FLJ20992 similar to


115816BE042915 Hs.287588 Homo Sapiens cD FLJ136755.55
fis, clone PL


128401801865 Hs.268586 ESTs 5.53


35 129296A1051967 Hs.110122 ESTs 5.53


120314T10013 Hs.221040 HBS1 (S. cerevisiae)-like5.51


132815AI815189 Hs.57475 sex comb on midleg homolog5.50
1


113983W87415 Hs.55296 HLA-B associated transcript-15.50


105002AA224244 Hs.182704 ESTs, Moderately similar5.49
~ to altertivel


40 132025AA011117 Hs.3745 milk fat globule-EGF 5.49
factor 8 protein


110732AW070838 Hs.174174 KIAA0601 protein 5.48


112891T03927 Hs.293147 ESTs, Moderately similar5.48
to A46010 X-tin


126758AI559444 Hs.293960 ESTs 5.48


129426AF077953 Hs.111323 Protein inhibitor of 5.47
activated STAT X


45 103217NM 001841Hs.73037 canbinoid receptor 2 5.46
(macrophage)


132261U80743 Hs.306094 irinucleotide repeat 5.45
containing 12


105586AA865118 Hs.191538 ESTs 5.43


109454AA232255 Hs.295232 ESTs, Moderately similar5.43
to A46010 X-tin


113063W15573 Hs.5027 ESTs, Weakly similar 5.43
to A47582 8-cell gr


134092AA218558 Ns.7905 sorting nexin 9 5.41


119316A1114630 Hs.208334 Homo Sapiens cD: FLJ218745.38
fis, clone H


108019A1017773 Hs.249159 adrenergic, alpha-2A-, 5.38
receptor


109421AW604652 Hs.332442 ESTs 5.38


111929AF027208 Hs.112360 prominin (mouse)-like 5.38
1


55 119718W69216 Hs.92848 ESTs 5.38


106154BE540255 Hs.6994 Homo Sapiens cD: FLJ220445.35
fis, clone H


108544W39433 Hs.23971 hypothetical protein 5.35
DKFZp547N043


119580AL079310 Hs.92260 high-mobility group 5.35
protein 2-like 1


126777AL157491 Hs.145211 Homo Sapiens m8; cD 5.35
DKFZp434K1111 (f


112944H18063 Hs.i3254 ESTs 5.34


103149NM 006201Hs.171834 PCTAIRE protein kise 5.34
1


132437AA152106 Hs.4859 cyclin L ania-6a 5.33


103860AW976877 Hs.38057 ESTs 5.33


104865T79340 Hs.22575 B-cell CLUlymphoma 6, 5.33
member 8 (zinc ft


65 129914NM 012421Hs.13321 rearranged L-myc fusion5.33
sequence


130309AF067804 Ns.15423 hypothetical protein 5.31
HDCMC04P


116312BE379794 Hs.65403 hypothetical protein 5.30


124191T96509 Hs.248543 ESTs, Moderately similar5.28
to S65657 alpha


125583AA195667 Hs.86022 ESTs 5.28


130591N59646 Hs.i69745 crumbs (Drosophila)homolog5.28
1


116355AA789133 Hs.88650 ESTs 5.26


115553AJ275986 Hs.71414 transcription factor 5.26
(SMIF gene)


122802AI687303 Hs.285529 G protein-ccupled receptor495.25


128495NM_005904Hs,fOQ602 MAD(mothersagainstdecapentaplegic,Dr5.24


117667U59305 Hs,44708 Ser-Thr protein kise 5.23
related to the my


127890AA294934 Hs.293902 ESTs, Weakly similar 5.22
to ISHUSS protein d


134843AA428520 Hs.90061 progesterone binding 5.21
protein


120968AA528283 Hs.292737 ESTs 5.21


102076BE299197 Hs.179665 cyclin-dependent lose 5.20
inhibitor 1A (p2


100934J03019 Hs.99913 adrenergic, beta-1-,receptor5.20


112667BE538516 Hs.15423 hypothetical protein 5.20
HDCMC04P


119304AW249266 Hs.98493 X-ray repair complementing5.20
defective rep


131868AW408296 Hs.33532 zinc finger protein 5.20
151 (pHZ-67)


102


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105914AW245680Hs.9701 growth arrest and D-damage-inducible,5.18


102258NM 001546Hs.34853 inhibitor of D binding 5.18
4, domint neg


103850AA187101Hs.213194 hypothetical protein 5.18
MGC10895


112516T83909 gb:yd67f10.r1 Snares 5.18
fetal liver spleen


133640AW246428Hs.75355 ubiquiGn-conjugating 5.18
enzyme E2N (homolo


135180D90070 Hs.96 phorbol-12-myristate-13-acetate-induced5.18


135309AI564123Hs.42500 ADP-ribosylation factor-like5.18
5


134801S76825 Hs.89695 insulin receptor 5.17


133362AK001519Hs.719d CGI-74 protein 5.17


135206AB024703Hs.96334 ring finger protein 11 5.15


111480806453 Hs.19706 ESTs 5.15


118466N66741 gb:yz33g08.s1 Morton 5.15
Fetal Cochlea Homo


125757AI274906Hs.166835 ESTs, Highly similar 5.15
to 1814460A p53-ass


127140AI273507Hs.303966 ESTs 5.15


1 109223AW000714Hs.65818 ESTs 5.14
5


103656273497 Hs.247802 Human D sequence from 5.14
clone U240C2 on


133388AW245631Hs.182447 heterogeneous nuclear 5.12
ribonucleoprotein


100511M76676 Hs.116840 ESTs 5.10


101941S77583 gb:HERVK101HUMMTV reverse5.10
hanscriptase


109937A1084066Hs.20072 myosin regulatory light 5.10
chain interactin


122996AI4362i6Hs.191715 ESTs, Weakly similar 5.10
to ZN91 HUMAN ZINC


128242AA992626Hs.269755 ESTs, Moderately similar5.10
to ALU5_HUMAN A


112374NM 016323Hs.26663 cyclin-E binding protein5.10
1


1245068E273688Hs.182447 heterogeneous nuclear 5.10
ribonucleoprolein


104216AB002313Hs.3989 plexin 82 5.09


135051AI272141Hs.83484 SRY (sex determining 5.08
region Y)-box 4


131629245794 Hs.238809 ESTs 5.08


111722823924 Hs.23596 EST 5.07


107034AF257770Hs.20930 poly(rC)-binding protein5.06
4


110243H26683 gb:y114g03.s1 Snares 5.05
breast 2NbHBst Homo


125837AW968123Hs.333513 small inducible cylokine5.05
subfamily E, me


130300X58288 Hs.154151 protein tyrosine phosphatase,5.05
receptor t


103967AL120051Hs.14d700 ephrin-B1 5.04


112678A1418466Hs.33665 ESTs 5.03


3 124963F06600 Hs.101375 Homo Sapiens m8; cD DKFZp434H2055.03
5 (fr


131379AK001123Hs.26176 hypothetical protein 5.03
FLJ10261


109451N32264 Hs.44330 ESTs 5.02


101396BE267931Hs.78996 proliferating cell nuclear5.02
antigen


131038W87778 Hs.169388 hypothetical protein 5.01
DKFZp761H2024


101208L25081 Hs.179735 ras homolog gene family,5.01
member C


104973NM 015310Hs.6763 KIAA0942 protein 4.99


103141X66113 Hs.75584 polymyosi6slscleroderma 4.96
autoantigen 2 (


111260AB033035Hs.51965 KIAA1209 protein 4.98


128142T67162 Hs.135127 ESTs, Weakly similar 4.98
to unmed protein


113857AW243i58Hs.5297 DKFZP564A2416 protein 4.96


105292AF128542Hs.166846 polymerase (D directed),4.96
epsilon


114341AF270491Hs.28249 hepatocellularcarcinoma-associated4.95
anti


100615W32474 Hs.301746 RAP2A, member of RAS 4.95
oncogene family


103208AW411340Hs.31314 retinoblastoma-binding 4.95
protein 7


121121AA399371Hs.189095 similar to SALLt (sat 4.95
(Drosophila)-like


125321T86652 Hs.178294 ESTs 4.95


101145L13210 Hs.79339 lectin, galactoside-binding,4.95
soluble, 3


100551M73980 Hs.129053 Homo Sapiens NOTCH 1 4.93
(N1) m8, complete


126182AA721331Hs.293771 ESTs 4.93


127925AA805151Hs.3628 mitogen-activated protein4.93
kise kise


133969AA669112Hs.78 GA-binding protein transcription4.93
factor,


120873AA358015 gb:EST66864 Fetal lung 4.92
III Homo Sapiens


125219AI804331Hs.99423 ATP-dependent R helicase4.91


102790BE245277Hs.154196 E4Ftranscriptionfactorl 4.90


129486NM 005754Hs.220689 Ras-GTPase-activating 4.90
protein SH3-domain


130381L47345 Hs.155202 transcription elongation4.89
factor B (SIII)


132389AA310393Hs.190044 ESTs 4.88


100260D38491 Hs.322478 KIAA0117 protein 4.88


109585N59650 Hs.27252 ESTs 4.88


111603811529 Hs.20634 EST 4.88


120514AA258335 gb:zr59b02.s1 Snares 4.88
NhHMPu-S1 Homo sapi


130314NM 014674Hs.154332 KIAA0212 gene product 4.86


108958AF142482Hs.203846 TEA domain family member4.86
3


126603W86610 Hs.185736 ESTs 4.85


100406A1962060Hs.118397 AE-binding protein 1 4.85


116238AV660717Hs.47144 DKFZP586N0819 protein 4.84


105288N99673 Hs.3585 ESTs, Weakly similar 4.83
to AF1267431 DJ


118753AA346206Hs.50471 ESTs, Weakly similar d.82
to T14267 Xin prote


113070A8032977Hs.6298 KIAA1151 protein 4.81


107908AF087999Hs.42826 ESTs d.80


119678A1658666Hs.6106 R binding motif protein 4.80
4


100415D86970 Hs.75822 TGFB1-induced anti-apoptotic4.79
factor 1


128360F12374 gb:HSC39B101 normalized 4.78
infant brain cDN


133101AK000299Hs.180952 dyctin d (p62) 4.78


g0 103507AJ000512Hs.296323 serom/glucocorticoid 4.78
regulated kise


107666AA010611Hs.60418 EST 4.78


108030AI378523Hs.62011 ESTs 4.78


131479D86181 Hs.273 galactosylceramidase 4.78
(Krabbe disease)


103


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133140AF1806B1Hs.6582 Rho guanine exchange 4.78
factor(GEF)12


134654AK001741Hs.8739 hypothetical protein 4.78
FLJ10879


106288AB037742Hs.24336 KIAA1321 protein 4.76


101524NM 000448Hs.73958 recombition activating 4.75
gene 1


113095AA828380Hs.126733 ESTs 4.75


114924A1338053Hs.87329 HSPC072 protein 4.75


127543AK000787Hs.157392 Homo Sapiens cD FLJ207804.75
fis, clone CO


115866AW062629Hs.52081 KIAA0867 protein ~ 4.75


101382AU076772Hs.1279 complement component 4.74
1, r subcomponent


1 126509847400 Hs.23850 ESTs 4.74
0


127930AA809672Hs.123304 ESTs 4.73


127824A1911516Hs.127811 ESTs 4.73


110049H12449 Hs.31159 EST, Weakly similar to 4.73
ALUB-HUMAN !!!! A


127115H77859 Hs.65450 reticulon 4 4.73


15 104727N81203 Hs.20047 zinc finger protein, 4.72
subfamily 2A (FYVE


127532AJ003429 gb:AJ003429 Selected 4.71
chromosome 21 cD


127304AI741577Hs.99962 proteoglycan 2, bone 4.70
marrow (lure) kit


105409AW505076Hs.301855 DiGeorge syndrome critical4.70
region gene 8


114969AWi62998Hs.24684 KIAA1376 protein 4.70


20 115125AA193588Hs.85888 ESTs 4.70


118348AW408586Hs.91052 ESTs, Moderately similar4.70
to ALUS-HUMAN A


123130AA487200 gb:ab19f02.s1 Stratagene4.70
lung (937210) H


130881AA809875Hs.25933 ESTs 4.70


132074AA478486Hs.3852 KIAA0368 protein 4.70


25 106897AF039023Hs.167496 RAN binding protein 6 4.69


131121AA720865Hs.23136 ESTs 4.69


116046BE395293Hs.94491 hypothetical protein 4.68
FLJ20297


112868AW388359Hs.10667 ESTs 4.68


116877AA708958Hs.168732 ESTs . 4.68


30 131241BE501914Hs.24654 Homo Sapiens cD FLJ116404.68
fis, clone HE


132027AF151020Hs.181444 hypothetical protein 4.68


133323BE336654Hs.70937 H3histonefamily,memberA 4.68


114269AA176769Hs.23450 mitochondria) ribosomal 4.67
protein S25


122713A1089443Hs.99436 ESTs 4.67


35 133571BE515037Hs.177556 melanoma antigen, family4.66
D,1


134453A1272141Hs.83484 SRY (sex determining 4.66
region Y)-box 4


115510BE299339Hs.72249 three-PDZcontaining protein4.66
similar to


115322L08895 Hs.78995 MADS boxtranscription 4.66
enhancerfactor2


129315NM 014563Hs.174038 spondyloepiphyseal dysplasia,4.65
late


40 104674AI935962Hs.26289 ESTs 4.65


106276AA625947Hs.25750 ESTs 4.65


108216AA524743Hs.44883 ESTs 4.65


120376AA227469 gb:zr18a07.s1 Stratagene4.65
NT2 neurol pr


121743AA397636 gb:zt79e09.r1 Soares 4.65
testis
NHT Homo sap


45 128011AI347067Hs.124636 - 4.65
ESTs


123454AA868510Hs.112496 ESTs 4.64


103409NM_004454Hs.43697 ets variant gene 5 (ets-related4.64
molecule


120484AA253170Hs.96473 EST 4.63


127046AA321948Hs.293968 ESTs 4.63


50 133164AA001021Hs.6685 thyroid hormone receptor4.63
interactor 8


123184BE247767Hs.18166 KIAA0870 protein 4.62


106627AK000706Hs.15125 hypothetical protein 4.61
FLJ20699


115475AB033085Hs.40193 hypothetical protein 4.61
KIAA1259


119468AI911535Hs.6657 hypothetical protein 4.59
bK1048E9.5


55 133662BE409053Hs.299629 peroxisomal long-chain 4.58
acyl-coA thioeste


113941AA531016Hs.22399 hypothetical protein 4.58
FLJ14824


131590846277 Hs.250638 Homo Sapiens m8 full 4.58
length insert cDN


128795AA531287Hs.105805 ESTs 4.58


116480C14088 Hs.169476 glyceraldehyde-3-phosphate4.58
dehydrogese


60 111713C75253 Hs.220950 ESTs 4.58


113721AF143885Hs.18190 EST 4.57


111657807364 Hs.268667 ESTs, Weakly similar 4.56
to ALU1 HUMAN ALU S


102009BE245149Hs.82643 protein tyrosine kise 4.55
9


135242AI583187Hs.9700 cyclin E1 4.55


65 127580BE548749Hs.148016 ESTs 4.55


109785A8011131Hs.12376 piccolo (presyptic cytomatrix4.53
protein)


109700F09609 gb:HSC33H092 normalized 4.53
infant brain cDN


124882AI698652Hs.10i539 ESTs 4.53


131765AW381270Hs.194110 hypothetical protein 4.53
PR02730


70 115684NM_006577Hs.284284 ESTs, Highly similar 4.52
to beta-1,3-N-acety


102034AI903474Hs.230 fibromodulin 4.52


109776843665 Hs.12257 ESTs 4.50


1 1 816722 Hs.124246 ESTs 4.50
1650


132993A8023154Hs.62264 KIAA0937 protein 4.49


75 129017AA115333Hs.107968 ESTs 4.49


132902A1936442Hs.59838 hypothetical protein 4.48
FLJ10808


114814AB006622Hs.182536 KIAA0284 protein 4.48


120839AA348913 gb:EST554421ntant adrel 4.48
gland II Homo


101434AV650066Hs.1430 coagulation factor XI 4.48
(plasma thrombopla


g0 102018003398 Hs.1524 tumor necrosis factor 4.48
(ligand) superfami


104619AA001635Hs.287414 transcriptiol intermediary4.48
factor 1 ga


106716AA931198Hs.238928 HT002 protein; hypertension-related4.48
calc


126020H79863 Ns.114243 ESTs 4.48


104


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
119899A1057404Hs.58698 ESTs 4.47


115582AW245047Hs.136164 cutaneous T-cell lymphoma-associated4.46
tum


125695W22529 Hs.30942 ephrin-82 4.46


105715BE621800Hs.29444 putative small membrane 4.45
protein NID67


117169887866 Hs.95120 ESTs, Weakly similar to 4.45
HZHU hemoglobin ,


102757AW955454Hs.30942 ephdn-82 4.45


120637AA811804 gb:ob39a05.s1 NCI-CGAP-GCB14.45
Homo Sapiens


131579N62922 Hs.290B8 ESTs 4.45


135287082670 Hs.9786 zinc finger protein 275 4.45


112540869751 gb:yi40at0.s1 Soares placenta4.45
Nb2HP Homo


125724AL360190Hs.295978 Homo Sapiens m8 full length4.44
insert cDN


115498AA291070 gb:zs46a08.s1 NCI CGAP 4.43
GCB1 Homo Sapiens


102263029171 Hs.75852 casein kise 1, delta 4.43


124312H94647 Hs.102329 ESTs 4.43


112366AF035318Hs.12533 Homo Sapiens clone 23705 4.43
m8 sequence


115955AF263613Hs.44198 inUacellularmembrane-associatedcalciu4.43


103562NM 002702Hs.2815 POU domain, class 6, transcdpfion4.42
facto


100169AL037228Hs.82043 D123 gene product 4.40


108928AA143802Hs.71781 ESTs 4.40


125908AF265555Hs.250646 baculoviral IAP repeat-containing4.40
6


126996BE161065Hs.167531 methylcrotonoyl-Coenzyme 4.40
A carboxylase 2


129512T88B45 Hs.112200 ESTs, Weakly similar to d.40
ALU7 HUMAN ALU S


134570066615 Hs.172280 SWIISNF related, matrix 4.d0
associated, acfi


135073W55956 Hs.94030 Homo Sapiens m8; cD DKFZp586E16244.40
(f


105011BE091926Hs.16244 mitofic spindle coiled-coil4.40
related prot


128793AB011125Hs.105749 KIAA0553 protein 4.40


107292BE166479Hs.4789 Homo sapiens serologically4.38
defined breas


126144H84455 Hs.40639 ESTs 4.38


130783X07282 Hs.171495 retinoic acid receptor, 4.3B
beta


30 135192083993 Hs.321709 purinergic receptor P2X, 4.38
ligand-gated 1o


100284D43767 Hs.66742 small inducible cytokine 4.37
subfamily A (Cy


117269N2i621 Hs.91142 KH-type splicing regulatory4.36
protein (FUS


104261AW248364Hs.5409 R polymerase I subunit 4.35


108609BE409857Hs.69499 hypotheficalprotein d.35


35 126319D81689 gb:HUM184E05B Human fetal4.35
brain (TFujiwa


127445AA906286Hs.193942 ESTs 4.35


130772BE270640Hs.19192 cyclin-dependentlose 2 4.35


134625AA977638Hs.184389 ESTs 4.35


135397L14922 Hs.i66563 replication factor C (activator4.35
1) 1 (14


40 128070AA886944Hs.303908 ESTs 4.35


135046AI494054Hs.93589 hypothetical protein DKFZp564B1162d.33


101881NM 004957Hs.754 folylpolyglutamate synthase4.33


129838AB007863Hs.185140 KIAA0403 protein 4.33


130974NM 003528Hs.2178 H2B histone family, member4.33
0


45 107763AA018220Hs.106730 chromosome 22 open reading4.32
frame 3


129818T71092 Hs.172572 hypothetical protein FLJ200934.31


129407AL137597Hs.11114 hypotheticalprotein dJ1181N3.14.30


110846BE277343Hs.297875 endoplasmic reticulum 4.30
chaperone SIL1, ho


111433801452 Hs.40193 hypothetical protein KIAA12594.30


50 114860AL157545Hs.42179 bromodomain and PHD fingerd.30
containing, 3


115853AW978561Hs.191548 ESTs 4.30


116165A1184751Hs.75874 pregncy-associated plasma4.30
protein A


126911AA428049Hs.1501 syndecan 2 (heparan sulfate4.30
proteoglycan


131230NM 005865Hs.274407 protease, serine,16 (thymus)4.30


55 100349D64110 Hs.77311 BTG family, member 3 4.29


100175BE258769Hs.32500 acetyl-Coenzyme A acyltransferase4.29
2 (mit


105335AW291165Hs.25447 ESTs 4.29


122507BE567620Hs.99210 ESTs 4.28


105397AA814807Hs.7395 hypothetical protein FLJ231824.28


133674AW851121Hs.75497 Homo Sapiens cD: FLJ221394.28
fis, clone H


102826NM 007274Ns.8679 cytosolic acyl coenzyme 4.28
A ihioester hydr


103272Ntv1_006680Hs.2838 malic enzyme 3, DP(+)-dependent,4.28
mitoc


111887838635 Hs.12328 KIAAi005 protein 4.28


120336N85785 Hs.181165 eukaryotic translation 4.28
elongation factor


65 133736D49958 Hs.75819 glycoprotein M6A 4.28


130356AF127577Hs.155017 nuclear receptor interacting4.27
protein 1


119830AW054922Hs.53478 Homo Sapiens cD FLJ12366 4.27
fis, clone MA


106758AB014564Hs.22616 KIAA0664 protein d.25


109709F09749 Hs.187405 ESTs 4.25


110463H52931 Hs.165067 ESTs 4.25


124472N52517 Hs.102670 EST 4.25


109770840322 Hs.248420 ESTs, Moderately similar 4.24
to A47582 B-cel


131487F13036 Hs.27373 Homo sapiens m8; cD DKFZp564017634.23
(f


107216D51069 Hs.211579 melanoma cell adhesion 4.23
molecule


75 123562AA177088Hs.190065 ESTs 4.23


125986W024i0 Hs.205555 ESTs 4.23


126221N20514 Hs.172965 ESTs 4.23


127092T26985 gb:NIBT065H01 R Infant 4.23
brain, LLNL array


132349AW975654Hs.181286 sedne protease inhibitor,4.23
Kazal type 1


118946N92834 gb:zb67f03.s1 Soares fetal4.22
lung-NbHLI9W


101531A1199711Hs.576 fucosidase, alpha-L- 1,Gssue4.21


105322T87179 Hs.16346 ESTs, Weakly similar to 4.21
557447 HPBRII-7


104219AB00232 3 Hs.7720 dynein, cytoplasmic, heavy4.20
polypeptide 1


105


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
102825BE262386Hs.7137 clones 23667 and 23775 4.20
zinc finger prate


103571AI675749Hs.211608 nucleoporin 153kD 4.20


106942AA995351Hs.31314 retinoblastoma-binding 4.20
protein 7


112685887650 Hs.33439 ESTs, Weakly similar 4.20
to ALU1_HUMAN ALU S


123107AA225048Hs.104207 ESTs 4.20


132659275190 Hs.54481 low density lipoprotein 4.20
receptor-related


130084AI929377Hs.173724 creative kise, brain 4.19


114553BE219860Hs.22505 hypothefical protein 4.18
FLJ 10159


129628036945 Hs.1174 cyclin-dependent kise 4.18
inhibitor 2A (me


102266029725 Hs.3080 mitogen-activated protein4.18
kise 7


110637AI241470Hs.268982 ESTs 4.18


127520T51239 gb:yb20d12.s1 Stratagene4.18
fetal spleen (9


130322NM-014247Hs.154545 PDZ domain containing 4.17
guanine nucleofide


104768082319 Hs.11056 RALBP1 protein 4.17


1 123360AA532718Hs.178604 ESTs 4.17
S


133110AA808177Hs.65228 ESTs 4.16


130923H96115 Hs.21293 UDP-N-acteylglucosamine 4.16
pyrophosphorylas


109878BE620775Hs.4866 Homo sapiens cD FLJ143874.16
fis, clone HE


119265BE539706Hs.285363 ESTs 4.16


124214H58608 Hs.151323 ESTs 4.15


106193AA057478Hs.23272 ESTs 4.15


105169BE245294Hs.180789 S164 protein 4.15


132304AA610002Hs.44296 hypothefical protein 4.15
FL122324


131600NM-004377Hs.29331 camiline palmitoyltransferase4.14
I, muscle


131365M93415 Hs.26014 activin A receptor, type4.14
II


121993AW297880Hs.98661 ESTs 4.14


110779A1391472Hs.12561 ESTs, Highly similar 4.13
to C212_HUMAN 28.3


126383AB032977Hs.6298 KIAA1151 protein 4.13


104446AF084555Hs.7351 cyclic AMP phosphoprotein,4.13
19 kD


131475AA992841Hs.27263 KIAA1458 protein 4.13


128933NM 002050Hs.334695 GATA-binding protein 4.12
2


113141AI493276Hs.9187 ESTs 4.11


134833L20965 Hs.89901 phosphodiesterase 4A, 4.11
CAMP-specific (dun


106461AI630759Hs.17481 Homo Sapiens clone 246064.10
m8 sequence


128056AI990131Hs.276973 potassium large conductance4.10
calcium-acli


114757AW970579Hs.291031 ESTs 4.10


134653A1765883Hs.87385 ESTs 4.09


100472D90084 Hs.1023 pyruvate dehydrogese 4.08
(lipoamide) alpha


103102X61177 Hs.68876 interleukin 5 receptor, 4.08
alpha


106779BE276013Hs.172364 Homo Sapiens m8 for FLJ000864.08
protein,


133615M62843 Hs.75236 ELAV (embryonic lethal, 4.08
abnormal vision,


130178020982 Hs.1516 insulin-like growth factor-binding4.07
prate


124659AI680737Hs.289068 Homo Sapiens cD FLJ119184.07
fis, clone HE


127861AW295020Hs.198529 ESTs 4.07


112129AB037715Hs.183639 hypothetical protein 4.07
FLJ10210


100918AK001335Hs.31137 protein tyrosine phosphatase,4.06
receptor t


124677801073 gb:ye84c03.s1 Soaresfetalliverspleen4.05


102722F13271 Hs.79981 Human clone 23560 m8 4.05
sequence


1 1 AB037721Hs.173871 KIAA1300 protein 4.05
1117


122506AA449120Hs.99209 ESTs 4.05


126392A1356294Hs.3280 caspase 6, apoptosis-related4.05
cysteine pr


130760AW379130Hs.18953 phosphodiesterase 9A 4.05


104220AB002324Hs.301094 KIAA0326 protein 4.05


112774895770 Hs.35455 ESTs 4.04


111128AW505364Hs.19074 lATS (large tumorsuppressor,4.04
Drosophila


113146BE151985Hs.5722 hypotheficalprotein FLJ233164.04


124940AF068846Hs.103804 heterogeneous nuclear 4.03
ribonucleoprotein


105498H68279 Hs.24937 transformer-2 alpha (htra-24.03
alpha)


112631882040 gb:yj06b06.s1 Scares 4.03
placenta Nb2HP Homo


118244N62516 Hs.48556 ESTs 4.03


118720N73515 gb:za49d07.s1 Soaresfetalliverspleend.03


129232898881 Hs.109655 sex comb on midleg (Drosophila)-like4.03
1


134192H01345 Hs.24139 Homo Sapiens cD: FLJ231374.03
fis, clone L


131893BE336886Hs.3416 adipose differentiafion-related4.02
protein


116793T77781 gb:yd20a11.s1 Soaresfetalliverspleen4.02


125674AL036166Hs.323378 coated vesicle membrane 4.01
protein


116640X89984 Hs.211563 B-cell CLLIlymphoma 7A 4.01


105057AA134233Hs.336942 Homo Sapiens cD: FLJ214884.00
fis, clone C


105158AW976357Hs.234545 hypothefical protein 4.00
NUF2R


116245A8033107Hs.42796 KIAA1281 protein 4.00


119946AA932283Hs.58925 ESTs 4.00


121975AA740679Hs.98631 ESTs 4.00


132037AA352702Hs.332541 Homo Sapiens, Similar 4.00
to RIKEN cD 2700


133669NM 006925Hs.166975 splicing factor, argininelserine-rich4.00
5


109468NM_015310Hs.6763 KIAA0942 protein 3.99


106829AW959893Hs.27099 hypothetical protein 3.99
FLJ23293 similar 1o


134682AW882645Hs.88044 sprouty (Drosophila) 3.98
homolog 1 (antagoni


105966AA142984Hs.5344 adaptor-related protein 3.98
complex 1, gamma


100448AF234887Hs.57652 cadhedn, EGF LAG seven-pass3.98
G-type rece


0 102589AU076728Hs.8867 cysteine-rich, angiogenic3.98
inducer, 61


104146AW880614Hs.146381 R binding mofif protein,3.98
X chromosome


111465AI968256Hs.15470 putafive ring zinc finger3.98
protein NY-REN


126499AK001779Hs.110445 CGI-97 protein 3.98


106


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
134388AW405434 Hs.82575 small nuclear ribonucleoprotein3.98
polypept


105564BE616694 Hs.28B042 hypotheticalprotein FLJ142993.g7


115206AW183695 Hs.186572 ESTs 3.96


103853AF272390 Hs.111782 myosin 5C 3.96
1


1 H58373 Hs.332938 hypothetical protein 3.96
0542 _ MGC5370


106797A1768801 Hs.169943 Homo Sapiens cD FLJ135693.96
fis, clone PL


130589AL110226 Hs.f6441 DKFZPd34N204protein 3.95


122786AI828638 Hs.99514 hypotheticalprotein FLJ205743.95


104518H20816 Hs.112423 Homo Sapiens m8; cD DKFZp5861f4203.95
130 (f


640 NM-004753Hs.17144 short-chain dehydrogeselreductase3.95
1


110847N30169 Hs.279807 ESTs, Weakly similar 3.95
to 2004399A chromos


116756AA46i045 Hs.50701 ESTs 3.95


122096AA431162 Hs.98690 ESTs 3.95


122160At769281 Hs.97d39 ESTs 3.95
1 123
5


930 AA740878 Hs.112982 ESTs 3.95


126280219417 gb:HS826B122 STRATAGENE 3.95
Human skeletal m


126547047732 Hs.84072 transmembrane 4 superfamily3.95
member 3


134757AA913267 Hs.211576 IL2-inducible T-cell 3.95
lose


117296AL133d27 Hs.42506 Homo Sapiens m8 full 3.95
112 length insert cDN


261 AL050297 Hs.300861 ESTs, Highly similar 3.95
to T08701 hypotheti


1 W39609 Hs.22003 solute camer family 6 3.94
t (neurotransmitle
2268


131844AI419294 Hs.324342 ESTs 3.94


101607X60111 Hs.1244 CD9 antigen (p24) 3.94


121613AA416879 Hs.193195 ESTs, Weakly similar 3.93
to 2109260A B cell.


115815AW905328 Hs.180842 ribosomal protein L13 3.93


125684AW589427 Hs.158849 Homo Sapiens cD: FLJ216633.93
fis, clone C


126783AA083531 gb:zn09d10.s1 Stratagene3.93
hNT neuron (937


129201H18359 Hs.109390 ESTs 3.93


128954AA346839 Hs.209100 DKFZP434C171 protein 3.92
1


22939AA477141 gb:zu37g06.s1 Soares 3.92
ovary tumor NbHOT H


130348AB032957 Hs.210850 KIAA1131 protein 3
92


125847AW161885 Hs.249034 ESTs .
3,g1


120452AL022328 Hs.104335 hypothetical protein 3.91
IMAGE35103t7


123143AA487595 gb:aa95e02.s1 5tratagene3,g1
10 fetal reti 93


5729 H46612 Hs.293815 Homo sapiens HSPC285 3.91
m8, partial cds


106605AW772298 Hs.21103 Homo Sapiens m8; cD DKFZp564B0763.90
(fr


126714AF114491 Hs.137354 egf-like module containing,3.90
mucin-like,


121611M31669 Hs.1735 inhibin, beta B (activin3.90
AB beta polypep


120468AW967675 Hs.96487 ESTs, Highly similar 3.90
1 to S08228 ribosomal
1


0 AW878229 Hs.80642 sigl transducer and activator3,gg
356 of traps


133668L7796d Hs.271980 mitogen-activated protein3,8g
kise 6


109114BE622787 Hs.84045 hypothetical protein 3.88
FLJ20288


115134AW968073 Hs.i94331 ESTs,HighlysimilarfoA55713inosito!3,8g


107850AA022910 Hs.295446 ESTs, Moderately similar3.88
to 810024C cyto


130907AA322866 Hs.2it07 neuroligin 3.88


101879AA176374 Hs.243886 nuclear autoantigenic 3,gg
sperm protein (his


104267AF043244 Hs.278439 nucleolar protein 3 (apoptosis3,gg
repressor


112232BE253927 Hs.24983 hypothetical protein 3.8g
from EUROIMAGE 2021


113248T63857 gb:yc16e01.s1 Stratagene3.88
1 lung (937210) H


14044BE327427 Hs.79953 ESTs 3.gg


115414AA662240 Hs.283099 AF15q14 protein 3.88


129598N30436 Hs.i 1556 Homo Sapiens cD FLJ125663.8g
fis, clone NT


102134AL036967 Hs.2324 protamine 2 3.87


106310898185 Hs.17240 ESTs 3.87



116470At272141 Hs.83484 SRY (sex determining 3.86
region Y)-box 4


110947AW298410 Hs.21475 ESTs 3
85


115839BE300266 Hs.28935 transducin-like enhancer.
of split 1, hom 3,g5


103534AW970672 Hs.9247 protein kise, AMP-activated,3.85
alpha 1 c


105209A8023197 Hs.227743 KIAA0980 protein 3.85
1


08749AA127017 Hs.71052 ESTs 3.85


110565A1884970 Hs.4983 ESTs 3.85


110799At089660 Hs.32340f dpy-30-like protein 3.85


117068H91257 Hs.41391 EST 3.85


130956NM 001135Hs.2159 aggrecan 1 (chondroitin 3.85
1 sulfate proteogl


02273BE391815 Hs.75981 ubiquitin specific protease3
14 (tR-gua 85


112960AL110209 Hs.6770 LCAT-like lysophospholipase.
3
84


114414AW152166 Hs.i82113 ESTs .
3
84


109665AA249439 Hs.27027 hypothetical protein .
DKFZp762H1311 84
3


106208AK001674 Hs.22630 cofactorrequiredfor Spi .
1 transcdptio 3,g4


22311NM-014913Hs.131915 KIAA0863 protein 3
84


124271AW293223 Hs.8928 hypothetical protein .
FLJ20291 3
83


106650AL049951 Hs.22370 Homo Sapiens m8; cD DKFZp56400122.
(f 3.83


112167N99591 Hs.255B7 ESTs, Weakly similar 3
to T00329 hypotheti 83


122354AL157579 Hs.153610 KIAA0751 gene product .
1 3.83
4


11 805296 gb:ye91e08.stSoaresfetalliverspleen3
62 g1


128109AW269421 Hs.128093 ESTs ,
3
81


127003AW816515 Hs.173540 ATPase, Class V, type ,
10D 3
81


109210AA669722 Hs.272137 ESTs .
3
81


132543BE568452 Hs.510i protein regulatorofcytokinesisl.
1 3.80


06827AA457456 Hs.11408 hypothetical protein 3
FLJ20435 80


124232H63391 Hs.339677 ESTs, Weakly similar .
(0138022 hypotheti 80
3


126039ALi37523 Hs.181102 p30 DBC protein .
3
80


128022AW195569 Iis.125906ESTs .
3.80


107


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
132005AA149707Hs.173091 ubiquitin-like 3 3.79


131392AA235153Hs.26320 TRABID protein 3.79


131775A8014548Hs.31921 KIAA0648 protein 3.79


126257N99638 gb:za39g11.r1 Soaresfetalliverspleen3.79


121950AA429515 gb:zw75c05.s1 Snares 3.79
testis_NHT Homo sap


116067AA454827Hs.293637 ESTs 3.78


104658AA360954Hs.27268 Homo sapiens cD: FlJ219333.78
fls, clone H


104493AW960427Hs.79059 Uansfortning growth factor,3.77
beta recepto


100163W44671 Hs.124 gene predicted from cD 3.77
with a complete


1 116223AF045458Hs.47061 unc-51 (C. elegans)-like3.77
~ lose 1


120586ALD31778Hs.797 nuclear transcription 3.76
factor Y, alpha


128764AW024282Hs.104938 hypothetical protein 3.75
MGC15906


111574A1024145Hs.188526 ESTs 3.75


117396W20128 Hs.296039 ESTs 3.75


15 119052810889 gb:yf38d02.s1Soaresfetalliverspleen3.75


121806AA424313Hs.984D2 ESTs 3.75


122410AA446854Hs.271004 ESTs, Weakly similar 3.75
to 138022 hypothefl


126638AA649257Hs.188602 ESTs 3.75


127879AA768098Hs.189079 ESTs 3.75


121095AA320134Hs.196029 Homo Sapiens m8 for KIAA16573.75
protein,


103430BE564090Hs.20716 Uansiocase of inner mitochondria)3.74
membr


101230AW504300Hs.295605 mannosidase, alpha, class3.74
2A, member 2


100200H94688 Hs.173737 ras-related C3 botulinum3.73
toxin subsfrate


106913AI219346Hs.86178 M-phase phosphoprotein 3.73
9


25 110975H17012 Hs.14633 ESTs 3.73


117314N32498 Hs.42829 ESTs 3.73


118737AA199686 gb:zq75g09.r1 SUatagene 3.73
hNT neuron (937


124169BE079334Hs.271630 ESTs 3.73


124580N68420 Hs.107992 ESTs . 3.73


125747NM 002884Hs.865 RAP1A, member of RAS 3.73
oncogene family


124879873588 Hs.101533 ESTs 3.72


128527AA504583Hs.101047 Uanscripflon factor 3 3.72
(E2A immunoglobul


103644M13305 Hs.247787 opsin 1 (cone pigments),3.72
long-wave-sensi


106044N90344 Hs.i49436 kinesin family member 3.71
58


35 127867C18530 gb:C18530 Human placentacD3.71
(fFujiwara


133828T28472 Hs.7655 U2 small nuclear dbonucleoprotein3.71
auxil


107387D86983 Hs.118893 Melanoma associated gene3.71


104160AA455706Hs.44581 heat shack protein hsp70-related3.71
protein


106098BE278344Hs.7970 DKFZP434B027 protein 3.70


40 133691M85289 Hs.211573 heparan sulfate proteoglycan3.70
2 (pedecan


120717AA904681Hs.154434 ESTs, Weakly similar 3.70
to unknown [H.sapie


119263T15977 gb:182328 Infant brain, 3.70
Bento Snares Hom


102305AL043202Hs.90073 chromosome segregation 3.70
1 (yeast homology


106566BE298210 gb:601118016F1 NIH_MGC_i73.70
Homo Sapiens c


45 110708N33878 Hs.306117 KIAA0306 protein 3.70


114357841677 Hs.6107 Homo Sapiens cD FLJ148393.70
fls, clone OV


1 AW972872Hs.293736 ESTs 3.70
15285


123034AL359571Hs.44054 ninein (GSK38 interacting3.70
protein)


126396T06298 Hs.153326 EST 3.70


132597Y11192 Hs.5299 aldehyde dehydrogese 3.70
5 family, member


105823AI559444Hs.293960 ESTs 3.70


102644T59816 Ns.173311 C18B11 homoiog (44.9kD) 3.70


133513AF136407Hs.1446 chromosome 6 open reading3.70
frame 5


116450AI654450Hs.47274 Homo Sapiens m8; cD DKFZp564B1763.69
(fr


55 104596AF067804Hs.15423 hypotheflcal protein 3.69
HDCMC04P


133579X75346 Hs.75074 mitogen-activated protein3.68
kise-activat


124556N29317 Hs.236463 Homo Sapiens m8; cD DKFZp586105213.66
(f


120534AI635113Hs.270366 ESTs, Weakly similar 3.68
to 178885 serinelth


10x1568E259039Hs.129953 Ewing sarcoma breakpoint3.68
region 1


134992AA464444Hs.5831 Ussue inhibitor of metalloproteise3.68
1


106730BE467313Hs.260707 ESTs 3.68


120680AA360240Hs.97019 EST 3.68


123731AA609839 gb:ae62f01.s1 SUatagenelung3.68
caroinoma


126973W46653 Hs.251928 nuclear pore complex 3.67
interacting protein


65 103646AW248439Hs.2340 junction plakoglobin 3.67


116333AF155827Hs.203963 hypothetical protein 3.67
FLJ10339


120922AA481003Hs.97128 ESTs 3.67


127407AW089514Hs.279681 heterogeneous nuclear 3.67
ribonucleoprotein


106578AA836381Hs.315111 nuclear receptor co-repressorIHDAC33.67
comp


123000AI584156Hs.105640 Homo Sapiens, clone IMAGE:4139775,3.67
m8,


101464AA852431Hs.51299 DH dehydrogese (ubiquinone)flavopro3.67


101397M26380 Hs.180B78 lipoproteinlipase 3.67


131135NM 016569Hs.267182 TBX3-iso protein 3.66


106112AL117518Hs.3686 KIAA0978 protein 3.66


75 123974NM 015678Hs.3821 neurobeachin 3.66


127742AW293496Hs.180138 ESTs 3.66


112908BE281000Hs.3530 TLS-associated serine-arginine3.66
protein 2


131802AL137406Hs.296356 Homo Sapiens m8; cD DKFZp434Mi623.65
(fr


135162AI187925Hs.95667 F-box protein 30 3.65


124984BE313210Hs.223241 eukaryotic Uanslaflon 3.65
elongation factor


118844AL035364Hs.50891 hypothetical protein 3.65


125429A1023654Hs.114191 ESTs 3.65


125596825698 gb:yg44h11.r2 Snares 3.65
infant brain 1N18 H


108


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125792AA496205Hs.193700 Homo Sapiens m8; cD DKFZp586103243.65
(f


126965AI470523Hs.139336 ATP-binding cassette, 3.65
sub-family C (CFTR


130776AF167706Hs.19280 cysteine-rich motor neuron3.65
1


131949AK000010Hs.258798 hypoihefical protein 3
FLJ20003 65


116612C14904 Hs.45184 Homo Sapiens cD FLJ12284.
fis, clone MA 3.65


123749AA609949Hs.112790 EST 3.65


134203AA161219Hs.799 diphtheria toxin receptor3.64
(heparin-bindi


133605AL038165Hs.75187 translocase of outer 3.64
mi(ochondriai membr


109235AI38i800Hs.300684 calcitonin gene-related 3
peptide-receptor 64


1 125447AI582222Hs.128686 ESTs .
0 3.63


122942A1277829Hs.111862 KIAA0590 gene product 3.63


122748AA458822Hs.193815 ESTs 3.63


103840AW975861Hs.47367 KIAA1785 protein 3.63


105333AA234831Hs.246112 KIAA0788 protein 3
63


15 108807A1652236Hs.49376 hypothetical protein .
FLJ20644 3.63


114699AA127386 gb:zn90d09.r1 Stratagene3.63
lung carcinoma


126040228444 Hs.24119 Homo Sapiens m8; cD DKFZp586G22223.63
(f


131028AI879165Hs.2227 CCAAT/enhancer binding 3.63
protein (CIEBP),


131710NM 015368Hs.30985 pannexin 1 3
63


100164AW372032Hs.173714 MORF-related gene X .
3.62


120837BE149656Hs.306621 Homo Sapiens cD FLJ119633.62
fis, clone HE


131089242645 Hs.22870 Homo Sapiens m8 full 3.62
length insert cDN


126428AA412436Hs.301985 ESTs 3.62


129148AW501216Hs.108945 KIAA0515 protein 3.61


102337AI814663Hs.170133 forkhead box 01A (rhabdomyosarcoma)3.61


104520A1702384Hs.76925 hypotheficalprotein FLJ149813.60


112954AA928953Hs.6655 Homo Sapiens EST from 3.60
clone 208499, full


125197AF086270Hs.278554 heterochromafin-like 3.60
protein 1


128124A1i25748Hs.130194 ESTs 3
60


30 129553AW015763Hs.113065 ESTs .
3.60


123998AA203429Hs.79474 tyrosine 3-monooxygeseltryptophan3.60
5-mo


128835AK001731Hs.106390 Homo Sapiens m8; cD DKFZp586H09243.59
(f


129226BE222494Hs.180919 inhibitor of D binding 3.59
2, dominl neg


135131AI582743Hs.94953 Homo sapiens, Similar 3.59
35 to complement comp


128955AA775076Hs.185807 Homo Sapiens, Similar 3.58
to PR00478 protein


100225D28539 Hs.167185 glutamate receptor, metabotropic3.56
5


101572AA437199Hs.656 cell division cycle 25C 3.58


102277031099 Hs.158326 prostaglandin D2 receptor3.58
(DP)


103667280788 Hs.247815 H4 histone family, member3.58
40 L


112373AW963357Hs.7847 ESTs 3.58


119284AL041224Hs.65379 ESTs 3.58


125422AA903229Hs.153717 ESTs 3.58


126381M76665 Hs.275215 hydroxysteroid (11-beta)3.58
dehydrogese 1


129168AI132988Hs.109052 chromosome 14 open reading3.58
45 frame 2


123133AA487264Hs.154974 Homo sapiens m8; cD DKFZp667N0643.57
(fr


128789AW368576Hs.139851 caveolin 2 3.57


104172AA476418 gb:zx02a12.s1 Soares 3.57
total_fetus-Nb2HF8_


134263AW973443Hs.8086 R (guanine-7-) methyltransferase3.57


101759M80244 Hs.184601 solute camerfamily 7 3
(cafionic amino 57


50 104942NM 016348Hs.10235 chromosome 5 open reading.
frame 4 3.56


123443BE244537Hs.i67382 triureticpeptidereceptorAlguanylate3.56


110707AI239832Hs.15617 ESTs, Weakly similar 3.55
to ALU4-HUMAN ALU S


106787AI492261Hs.32450 ESTs 3.55


112940AK001757Hs.281348 hypothetical protein 3.55
55 FLJ10895


115301Ti 1832 Hs.127797 Homo sapiens cD FLJ113813.55
fis, clone HE


125978N66843 Hs.35608 ESTs 3.55


128002AI985897Hs.125293 ESTs 3.55


119847H81136 Hs.334604 Homo Sapiens m8 for KIAA18703.55
protein,


13,4595NM 002401Hs.29282 mitogen-activated protein3.55
60 lose kise


121309AA293834Hs.97312 ESTs 3.54


122679AA811286Hs.192837 ESTs, Weakly similar 3.54
to ALU5_HUMAN ALU S


106061AA565356Hs.13250 ESTs 3,54


127207AA377165Hs.44833 ESTs 3,54


129563AF119664Hs.27299 transcripfiol regulator 3.54
65 protein


105951848700 Hs.20733 Homo Sapiens cD: FLJ223563.53
fis, clone H


115643AA404276Hs.123253 hypothetical protein 3.53
FLJ22009


130473011690 Hs.1572 faciogenital dysplasia 3.53
(Aarskog-Scott sy


104246AF016032Hs.201377 lysosomal 3.53


120562BE244580Hs.302267 hypothefical protein 3.53
70 1 FLJ10330


01211 AA355357Hs.283429 SMC (mouse) homolog, 3.53
X chromosome


100774J05581 Hs.89603 mucin 1, iransmembrane 3.53


108407AA075519 gb:zm87h09.s1 SUatagene 3.53
ovarian cancer


113538AI554947Hs.15167 ESTs, Weakly similar 3.53
to S37482 finger pr


113876AI799751Hs.5635 ESTs 3
53


75 110731NM 014899Hs.188006 KIAA0878 protein .
3.52


125845AK001440Hs.131840 hypothetical protein 3.51
FLJ10578


112945AW138458Hs.20787 Homo Sapiens cD: FLJ216863.51
fis, clone C


131686NM 012296Hs.30687 GRB2-associated binding 3.51
protein 2


125413AI887951Hs.74566 dihydropyrimidise-like 3.51
$0 3


129360AJ000534Hs.110708 sarcoglycan, epsilon 3.50


128819838007 Hs.77578 ubiquitin specific protease3.50
9, X chromos


101973041514 Hs.80120 UDP-N-acetyl-alpha-D-galactosamine:polyp3.50


103616NM_002647Hs.32971 phosphoinositide-3-kise,3.50
class 3


109


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
105535AI459519 Hs.297681serine (or cysteine) proteise3.50
inhibito


118767A1038653 Hs.50500 ESTs 3.50


126634AW361109 Hs.43627 SRY (sex determining region3.50
Y)-box 22


130851866282 Hs.20247 ESTs, Weakly similar to 3.50
S65657 alpha-1 G


134353AL138201 Hs.82120 nuclear receptor subfamily3.50
4, group A, m


111394AA412227 Hs.16131 hypothetical protein FLJ128763.50


102696BE540274 Hs.239 forkhead box M1 3.49


113037817268 Hs.259873axol transport of sypfic 3.49
vesicles


111028H59346 Hs.30151 ESTs, Weakly simitar to 3.49
1 1 138022 hypothefi
O 1


688 AI935413 Hs.30692 p21 (CDKN1A)-acfivated 3.49
3 kise 2


115613AW136951 Hs.173946hypothetical protein FLJ104863,qg


1f6975H81076 Ns.269001ESTs 3,qg


100210D26361 Hs.3104 KIAA0042geneproduct 3.48


110147H18700 Hs.268799ESTs 3.48
15 11
6


AA081395 Hs.42173 Homo Sapiens cD FLJ10366 3.48
00 fis, clone NT


119088839261 Hs.90790 Homo Sapiens cD: FLJ22930 3.48
fis, clone K


120347AA211068 Hs.120247nuclear fragile X mental 3.48
retardation pro


122702AI2200B9 Hs.99439 ESTs 3.48


125552H09701 Hs.278366ESTs, Weakly similar to 3.48
126 138022 hypotheG


461 AI381659 Hs.267086ESTs 3.48


128572AA933022 Hs.256583inferieukin enhancer binding3.48
factor 3, 9


118397BE139479 Hs.161492ESTs 3.47


127999AW978827 Hs.69851 nucleolar protein family 3.47
A, member 1 (HI


132066A1929392 Hs.181195DJ (Hsp40) homolog, subfamily3.47
1056 B, membe


93 BE250951 Hs.181368U5 snRNP-specific protein 3.47
(220 kD), orth


128874H06245 Hs.106801ESTs, Weakly similar to 3.46
PC4259 ferrifin


119984AA230228 Hs.59197 ESTs 3.46


104000A1146527 Hs.80475 polymerase (R) II (D directed)3.46
polyp


101488BE547216 Hs.181128ELKt, member of ETS oncogene3.46
1 family


J05614 gb:Human proliferafing 3.46
045 cell nuclear anG


120149AA227609 Hs.94834 ESTs 3.46


107025AA825523 Hs.21255 ESTs, Weakly similar to 3.45
138022 hypotheti


101716AF050658 Hs.2563 tachykinin, precursor 1 3.45
(substance K, su


1D2899AI815559 Hs.75730 sigl recognifion parficle 3.45
3 1230 receptor ('d
5


75 AW293133 Hs.101340ESTs, Weakly similar to 3.45
A42442 integrin


124695AA594979 Hs.239307tyrosyl-tRsynthetase 3.45


127669N28989 Hs.22891 solute carrier family 7 3.45
(cationic amino


129793AW207000 Hs.126857Homo Sapiens cD FLJ12936 3,44
fis, clone NT


120095AA693774 Hs.59601 ESTs 3.qq
10


1 BE0922B5 Hs.29724 hypothetical protein FLJ131873.43
915


130542064675' Hs.179825RAN binding protein 2-like3.43
1


100488BE273749 Hs.752 FK506-binding protein 1A 3.43
(12kD)


115027AA743331 Hs.272572hemoglobin, alpha 2 3.43


119298NM 001241Hs.155478cyclin T2 3.43
45


126486A1065133 Hs.152316hypothetical protein PR009713.43


13(1021M24470 Hs.1435 guanosine monophosphate 3.43
reductase


127166AW954605 Hs.263395sema domain, transmembrane3.42
domain (TM),


114988AA251089 gb:zs04f05.s1 NCI-CGAP_GCBt3.42
Homo Sapiens


133817AW578716 Hs.7644 H1 histone family, member 3.41
5~ 2


133562M60721 Hs.74870 H2.0 (Drosophila)-like 3.41
homeo box 1


105610AA280072 Hs.99872 fetal Alzheimer antigen 3.41


129007AK00i521 Hs.107882hypothetical protein FLJ106593.41


100662AI368680 Hs.816 SRY (sex determining region3.41
Y)-box 2


120159860781 Hs.92927 putative 47 kDa protein 3.41
SJr1349


66 AWd02389 Hs.920 modulator recognition factor!3.41


100369D79988 Hs.115778KIAA0166 gene product 3.41


10426()AF008192 Hs.194283putative GR6 protein 3.40


10D134AA305746 Hs.49 macrophage scavengerreceptori3.40


116015AA338648 Hs.50334 testes development-related3.d0
119 NYD-SP22


251 T15753 Hs.65250 EST 3.40


127176BE387162 Hs.280858ESTs, Highly similar to 3.40
A35661 D excis


123422AA598484 gb:ae38f04.s1 Gessler Wilms3.39
tumor Homo s


123094AA761073 Hs.146847TRAF family member-associated3.39
NFKB acfiv


105289A8020638 Hs.103000KIAA0831 protein 3.39
65 111


219 N68836 Hs.19247 ESTs, Moderately similar 3.38
to ALUC HUMAN !


127963AI299013 Hs.87779 Homo Sapiens cD: FLJ23087 3.38
fis, clone L


109412BE543313 Hs.209473hypothetical protein FLJ105203.38


118794AW517051 Hs.118210ESTs 3.38


112040843286 gb:ygi7eit.sl Soares infant3.38
brain iNlB H


111180AI798851 Hs.283108hemoglobin, gamma G 3.38


117329AA524065 Hs.93670 Homo Sapiens cD: FLJ22664 3.38
fis, clone H


104371AI288696 Hs.194081ESTs, Weakly similar to 3.38
138022 hypothefi


109265AA195285 Hs.85982 ESTs 3.38


109557AW452405 Hs.6427 ESTs 3.38
75 1 1


20753AA3 Hs.230157ESTs 3.38
2551


120970AA398118 Hs.97579 ESTs, Weakly similar to 3.38
A46010 X-linked


127094F13215 Hs.287849ESTs, Weakly similar to 3.38
T22074 hypothefi


127746AI239495 Hs.120i89ESTs 3.38


123553AI49429f Hs.11f977ESTs 3.37


130652M31669 Hs.1735 inhibin, beta B (acfivin 3.37
AB beta polypep


135101082275 Hs.94498 leukocyte immunoglobulin-like3.37
receptor,


121799AI885670 Hs.124027SELENOPHOSPHATE SYNTHETASE3.37
; Human selen


112278241698 Hs.26039 Homo Sapiens cD FLJ13937 3.36
fis, clone Y7


110


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
113401AA610175 Hs.179647Homo Sapiens cD FLJ12195 3.36
fis, clone MA


109292AW975746 Hs.188662KIAA1702 protein 3.36


135026N92165 Hs.93231 ESTs 3.36


118210N49233 Hs.46914 ESTs, Weakly similar to 3.35
A46010 X-linked


123476AA384564 Hs.108829ESTs 3.35


111076N59129 Hs.20851 ESTs 3.35


111520AI985369 Hs.301134ESTs 3.35


133383BE313555 Hs.7252 KIAA1224 protein 3.35


103731AA070545 gb:zm70c03.ri Stratagene 3.35
1 neuroepithelium
~


110828AK002114 Hs.23495 hypoiheficalprotein FLJi12523.35


112520868654 Hs.30814 ESTs 3.35


115725AW899053 Hs.76917 F-box only protein 8 3.35


125867H13331 Hs.123721ESTs 3.35


127719A1242163 Hs.22670 chromodomain helicase 3.35
D binding protei


1 129863BE379765 Hs.129872sperm associated anfigen 3.35
9


130816M61877 Hs.1985 specUin, alpha, eryihrocytic3.35
1 (ellipto


130888AL044315 Hs.173094Homo Sapiens m8 for KIAA17503.35
protein,


133377AJ131245 Hs.7239 SEC24 (S. cerevisiae) 3.35
related gene Tamil


118986AF148713 Hs.125830bladdercanceroverexpressed3.35
protein


101723034304 gb:Human nonmuscle myosin3.34
heavy chain II


134693N70361 Hs.8854 Human transcripfion unit 3.34
PVT gene, exons


102856M26150 Hs.248177H3 histone family, member3.34
L


105593AA279341 Hs.174151aldehyde oxidase 1 3.34


134748L34059 Hs.8948d cadherin 4, type 1, R-cadherin3.34
(retil)


25 109149AA831179 Hs.400fi5hypothefical protein MGC48253.33


115026AA251972 Hs.188718ESTs 3.33


103546214244 Hs.75752 cytochrome c oxidase subunitVllb3.33


111189N67603 Hs.272130ESTs, Weakly similar to 3.33
S65824 reverse t


127076AI422951 Hs.146162ESTs 3
33


30 124949A1903210 Hs.336780tubulin, beta polypeptide.
3.33


111012A1077389 Hs.269818ESTs, Weakly similar to 3.33
2195-HUMAN ZINC


113412AW628660 Hs.44131 KIAA0974 protein 3.33


116351AL133623 Hs.82501 similar to mouse Xm1 t 3.33
Dhm2 protein


121633AA417011 Hs.98175 EST 3
33


35 124591N69243 Hs.192974hypothetical protein FLJ12735.
3.33


130225AB021179 Hs.15299 HMBA-inducible 3.33


131945NM 002916Hs.35120 replication factor C (activator3.33
1) 4 (37


132561AK000631 Hs.52256 hypothetical protein FLJ206243.33


105726NM 012068Hs.9754 activating transcription 3
factor 5 32


101867M96132 gb:Human MHCclass It HLA-DR-beta-1*090i.
3.32


105004BE616023 Hs.25298 KIAA1813 protein 3.32


100288AL039103 Hs.153834pumilio (Drosophila) homolog3.32
1


118349N63786 Hs.94149 ESTs, Weakly similar 1o 3.32
ALU1_HUMAN ALU S


103352H09366 Hs.78853 uracil-D glycosylase 3.30


45 107436W27720 Hs.12450 protocadherin 9 3.30


109062AA160941 gb:zq40d12.s1 Stratagene 3.30
hNT neuron (937


110379AI300505 Hs.33130 Homo Sapiens cD: FLJ234863.30
fis, clone L


111221AB037782 Hs.15119 KIAA1361 protein 3.30


117903AA768283 Hs.47111 ESTs 3
30


123265AA491209 gb:aa47a08.s1 NCI_CGAP-GCBs.
Homosapiens 3.30


128226AI284940 Hs.289082GM2 ganglioside activator3.30
protein


111945840663 Hs.124944ESTs 3.30


126214AW748336 Hs.168052KIAA0421 protein 3.30


121073H46199 Hs.112184DKFZP586J0619 protein 3
30


55 102083T35901 Hs.75117 interleukin enhancer binding.
factor 2, 4 3.30


100992NM-007289Hs.1298 membrane metallo-endopepfidase3.30
(neutral


134021L13720 Hs.7850i growth arrest-specific 3.30
6


126452826867 .gb:yh52e01.s1 Soares 3.29
placenta Nb2HP Homo


7195 AI798425 Hs.42710 ESTs 3
11 29


, AK000452 Hs.10340 hypothefical protein FLJ20445.
127663 3.29


113677270200 Hs.246112KIAA0788 protein 3.28


132398AA876616 Hs.16979 ESTs, Weakly similar to 3.28
A43932 mucin 2 p


109533AL043979 Hs.259729KIAA0596 protein 3.28


102915X07820 Hs.2258 matrix mefailoproteise 3.28
10 (stromelysin


6Jr104348H05405 Hs.19221 hypothetical protein DKFZp566G14243.28


113047AI571940 Hs.7549 ESTs 3.28


113203AA743563 Ns.10305 ESTs 3.28


114503AL040600 Hs.188083ESTs 3.28


122100AA431220 Hs.410fi6pleckstrin homology domain-containing3.2fi
f


123073AA485061 Hs.105652, 3.28
ESTs


130253A1078570 Hs.167473phosphoglucomutase 5 3.28


130365W56119 Hs.155103eukaryotic translation 3.28
initiation factor


130762D84371 Hs.1898 paraoxose 1 3.28


132360AW893660 Hs.46440 solute camer family 21 3.28
(organic anion


75 110763AI928445 Hs.92254 syplotagmin-like 2 3.27


103437AV655598 Hs.184211peptidase (mitochondria) 3.27
processing) bet


114840AA447591 Hs.87359 ESTs, Highly similar to 3.27
RB18_HUMAN RAS-R


106888AA020964 Hs.24734 oxysterol binding protein3.27


129896BE29S568 Hs.13225 UDP-GahbetaGlccbetal,4-galactosyll3.26


113459T80206 Hs.i4716 ESTs 3.26


134332D86962 Hs.81fi75growth factor receptor 3.26
bound protein i0


117048H89732 Hs.230113EST 3.26


109249AA194730 Hs.268189hypothetical protein FLJ204363.26


111


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
134663W73428 Hs.8750 uncharacterized bone 3.26
marrow protein BM04


114440AL046511Hs.106525 hypoiheticalprotein FLJ125673.25


102196BE266830Hs.75238 chromatin assembly factor3.25
1, subunit B (


109581845584 Hs.23025 ESTs, Weakly similar 3.25
to ALUS HUMAN ALU S


120814AW867796Hs.96860 ESTs, Weakly similar 3.25
to 138022 hypotheG


122391AA446316Hs.191622 ESTs 3.25


122553AA451884Hs.190121 ESTs 3.25


124755838087 Hs.267690 KIAA1228 protein 3.25


130943020760 Hs.272429 calcium-sensing receptor3.25
(hypocalciuric


1 115185BE299677Hs.105461 hypothetical protein 3.25
~ FLJ20357


114297AA149707Hs.173091 ubiqui6n-like 3 3.25


106657AW854339Hs.33476 hypothetical protein 3.25
FLJ11937


124320H95749 Hs.102342 EST 3.25


124087HOB773 Hs.288590 Homo Sapiens cD FLJ114543.24
fis, clone HE


1 110705AB007902Hs.32168 KIAA0442 protein 3.24



106508A1205785Hs.30348 ESTs 3.24


112538AA908813 gb:og77hO6.s1 NCI CGAP_Ov83.24
Homo sapiens


100130NM 000304Hs.103724 peripheral myelin protein3.24
22


106017AA477956Hs.26268 ESTs -- 3.24


2~ 113921AW976530Hs.28355 hypothetical protein 3.23
FLJ22402


121520AA412163Hs.164785 ESTs 3.23


129255A1961727Hs.109804 H1 histone family, member3.23
X


125069H81306 Hs.194485 ESTs 3.23


119863AA081218Hs.58608 Homo Sapiens cD FLJ142063.23
fis, clone NT


25 111273N70934 gb:za33fO6.s1 Soaresfetalliverspleen3.23


102971X16609 Hs.183805 ankyrin 1, erythrocytic 3.23


103937AA934063Hs.13836 ESTs, Weakly similar 3.23
to 138022 hypotheG


121770NM 015902Hs.278428 progestininduced protein3.23


128972AA528140Hs.107515 ESTs, Weakly similar 3.23
to T00329 hypotheti


132528T78736 Hs.50758 SMC4 (structural maintence3.23
of chromoso


134835L04569 Hs.89925 calcium channel, voltage-dependent,3.23
L ty


103158BE242587Hs.118651 hematopoietically expressed3.22
homeobox


118405AL117518Hs.3686 KIAA0978 protein 3.22


104631AA002064Hs.18920 ESTs 3.22


3 114253BE149866Hs.14831 Homo Sapiens, Similar 3.22
5 to zinc finger pro


134607AI675881Hs.86538 ESTs 3.22


135114AW340493Hs.175043 ancient conserved domain3.22
protein 4


120191BE407106Hs.65907 Homo Sapiens, clone IMAGE:3959816,3.22
m8,


105029A1122691Hs.13268 ESTs 3.21


128550AA418276Hs.170142 ESTs 3.21


119873A1660149Hs.44865 lysosomal 3.21


130115T47294 Hs.149923 X-box binding protein 3.21
1


133916AL039185Hs.77558 thyroid hormone receptor3.21
interactor 7


120259AW014786Hs.192742 hypothetical protein 3.21
FLJ12785


45 110721H97678 Hs.31319 ESTs 3.21


130062AL049415Hs.278679 a disintegrin and metalloproteise3.21
doma


100265D38521 Hs.112396 KIAA0077 protein 3.20


100624AB001025Hs.9349 ryanodinereceptor3 3.20


122275AA437124Hs.187247 ESTs 3.20


127099AA347668 gb:EST54026 Fetal heart 3.20
II Homo Sapiens


134321BE538082Hs.8172 ESTs, Moderately similar3.20
to A46010 X-lin


132809AF036144Hs.5734 meningioma expressed 3.20
antigen 5 (hyaluron


101125AJ250562Hs.82749 transmembrane 4 superfamily3.20
member 2


128339AL121087Hs.296406 KIAA0685 gene product 3.19


5 117121H95044 Hs.32i386 EST 3.19
5


124760AW408586Hs.91052 ESTs, Moderately similar3.19
to ALU5_HUMAN A


132232AI522273Hs.42640 ESTs 3.19


125919W26713 Hs.256972 ESTs 3.19


123324A8018352Hs.105399 KIAA0809 protein 3.19


100157D14661 Hs.119 Wilms'tumourl-associating3.19
protein


101447M21305 gb:Human alpha satellite3.19
and satellite 3


124345NM 014487Hs.120766 nucleolarcysieine-rich 3.18
protein


122583NM 012447Hs.20132 stromal antigen 3 3.18


128961AL133014Hs.107387 CGI-20 protein 3.18


65 111321AI569766Hs.13205 ESTs ~ 3.18


134977AL044963Hs.306121 leukocyte receptorcluster(LRC)encoded3.18


131535N22120 Hs.75277 hypothetical protein 3.18
FLJ13910


109950H08200 Hs.268770 ESTs, Weakly similar 3.18
to 2004399A chromos


129875AA181018Hs.13056 hypothe6calprotein FLJ139203.18


7~ 101654M60298 Hs.733 erythrocyte membrane 3.18
protein band 4.2


104732AL079294Hs.29952 Homo Sapiens m8 full 3.18
length insert cDN


106867AB037744Hs.34892 KIAA1323 protein 3.18


108301AA069728Hs.184582 ribosomal protein L24 3.18


118042AI432389Hs.161465 ESTs 3.18


7S 120900AA830712Hs.291931 ESTs 3.18


129312T97579 Hs.110334 ESTs, Weakly similar 3.18
to 178885 serinelth


116291AW410377Hs.41502 hypothetical protein 3.17
FLJ21276


110672AW612890Hs.191178 ESTs 3.17


115665BE072425Hs.44579 hypothetical protein 3.17
FL120199


127581AK000680Hs.266175 phosphoprotein associated3.17
with GEMS


129584AV656017Hs.184325 CGI-76 protein 3.16


108830AA131743Hs.193352 ESTs 3.16


124443A1857519Hs.302031 zinc finger protein, 3.16
subfamily 1A, 4 (Eo


112


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
106290AW961393 Hs.16364 hypothetical protein 3.16
FLJ10955


122787AI209093 Hs.99512 ESTs 3.16


133112T15465 Hs.182231thyrotropin-releasing 3.16
hormone


116435AA186761 Hs.334812hypothetical protein 3.16
DKFZp586K0717


109121BE389387 Hs.49767 DH dehydrogese (ubiquinone)3.16
Fe-S pro


126721AW579621 Hs.125359Thy-1 cellsurface antigen3.15


102526AA203429 Hs.79474 tyrosine 3monooxygeseltryptophan3.15
5-mo


100512D13317 Hs.78915 GA-binding protein transcription3.15
factor,


105299AF098951 Hs.19d720ATP-binding cassette, 3.15
sub-family G (WHIT


1 117842AI984505 Hs.161121ESTs 3.15
~


123049BE047680 Hs.211869dickkopf (Xenopus laevis)3.15
homolog 2


128639AW582962 Hs.102897CGI-47 protein 3.15


130343AB040914 Hs.278628KIAA1481 protein 3.15


115706AB004849 Hs.50748 chromosome 21 open reading3.15
frame 18


1 120673AW968634 Hs.105093ESTs 3.15
J~


132116AW960474 Hs.40289 ESTs 3.15


116217AU076474 Hs.123178translocase of inner 3.15
mitochondria) membr


104926BE298808 Hs.33363 DKFZP434N093 protein 3.14


105297NM 015905Hs.183858transcrtptiol intermediary3.14
factor 1


125343AI475495 Hs.304101ESTs, Weakly similar 3.14
to ALU7_HUMAN ALU S


115618H11695 Hs.322901disrupter of silencing 3.14
10


124893AA830185 Hs.269680ESTs 3.13


105461BE539071 Hs.69388 hypothetical protein 3.13
FLJ20505


126165AI7418i6 Hs.125897ESTs 3.13


105212AA205334 Hs.324278Homo sapiens m8; cD DKFZp566M0633.13
(fr


101628M57506 Hs.72918 small inducible cytokine3.13
A1 (I-309, homo


107951AI300077 Hs.6i590 ESTs 3.13


109166AA219691 Hs.73625 RA86 interacting, kinesin-like3.13
(rabkines


117299N75768 gb:yw30b07.r1 Morton 3.13
Fetal Cochlea Homo


3 119694AA041350 Hs.57847 ESTs, Moderately similar3.13
~ to ICE4 HUMAN C


124840856146 Hs.164515EST, Weakly similar to 3.13
AF0909301 PR0047


127433AW979155 Hs.298275amino acid transporter 3.13
2


128337AI123529 Hs.166592ESTs 3.13


134053AW628686 Hs.78851 KIAA0217 protein 3.13


35 134475NM 014733Hs.83790 KIAA0305 gene product 3.13


128761BE300341 Hs.104925ectodermal-neural cortex3.12
(with BTB-like


124971T23800 Hs.151001hypothetical protein 3.12
FLJ14728


128314T87479 Hs.291797ESTs 3.12


134695A8036829 Hs.178347SKIP for skeletal muscle3.12
and kidney enri


131333BE244603 Hs.25726 transposon-dertved Busterltransposase-I3.12


119781AJ278016 Hs.55565 ankyrin repeat domain 3.12
3


131824028838 Hs.32935 TATA box binding protein3.11
(TBP)-associate


124595AW194851 Hs.111801arsete resistance protein3.11
ARS2


116115AL042355 Hs.70202 WD repeat domain 10 3.11


45 129415AI907084 Hs.111243MADS box transcription 3.11
enhancer factor 2


111552T97939 Hs.191185ESTs 3.10


134861NM Hs.171880polymerase (R) II (D 3.10
000937 directed) polyp


104971- Hs.15830 hypothetical protein 3.10
BE311926 FLJ12691


126536AA156151 gb:zo48cO6.r1 Stratagene3.10
endothelial ceI


128246AI990612 Hs.214818DMRT-like family C2 3.10


106412AA453734 Hs.10198 ESTs 3.10


107902AA026627 Hs.61358 ESTs 3.10


112495A1346487 Hs.28739 ESTs 3.09


131870NM 014874Hs.3363 KIAA0214 gene product 3.09


55 105301AW352357 Hs.7457 MAGEi protein 3.09


123670AI189844 Hs.112708ESTs, Moderately similar3.09
to ZN91 HUMAN Z


116474AW160774 Hs.159154tubulin, beta, 4 3.09


112064AL049390 Hs.22689 Homo sapiens m8; cD DKFZp586013183.09
(f


130525AA361850 Hs.322149Human clone 137308 m8, 3.08
partial cds


60 120398AL133649 Hs.110953retinoic acid induced 3.08
1


102735AF111106 Hs.3382 protein phosphatase 4, 3.08
regulatory subuni


124748R346i7 gb:yh85h12.s1 Soares 3.08
placenta Nb2HP Homo


120755AA312934 Hs.190745Homo Sapiens cD: FLJ213263.06
fis, clone C


118895BE304917 Hs.31097 hypothetical protein 3.08
FLJ21478


65 107463AW952022 Hs.315164hypothetical protein 3.08
similar to actin re


114290851383 Hs.25793 ESTs 3.06


119005AL038511 Hs.125316ESTs, Weakly similar 3.08
to S33990 finger pr


125676BE612918 Hs.151973hypothetical protein 3.08
FLJ23511


127766AA723659 Hs.290607EST 3.08


132693BE244200 Hs.55075 KIAA0410 gene product 3.07


106812BE251590 Hs.239370DKFZP7271051 protein 3.07


125654X96753 Hs.9004 chondroitin sulfate proteoglycan3.07
4 (mela


111836858394 Hs.25119 ESTs, Weakly similar 3.06
to YEXO-YEAST HYPOT


101682AF043045 Hs.81008 filamin B, beta (actin-binding3.06
protein-2


75 110004H104i3 Hs.268774ESTs 3.06


117591N64777 Hs.44656 ESTs 3.06


110737AA335609 Hs.7589 ESTs, Weakly similar 3.06
to A46010 X-linked


134337NIvL004922Hs.81964 SEC24 (S. cerevisiae) 3.06
related gene famil


132450AA100012 Hs.48827 hypothetical protein 3.06
FLJ12085


go 125556A8033064 Hs.334806KIAA1238 protein 3.06


101811NM 002556Hs.24734 oxysterol binding protein3.06


131530AA574309 Hs.283402TCR eta 3.06


105049AB032945 Hs.172506myosin VB 3.06


113


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
126614AA701941 Hs.187555 ESTs 3.05


130960AF035621 Hs.21611 kinesin family member 3C 3.05


105503AW963624 Hs.31707 ESTs, Weakly similar to YEW4
YEAST HYPOT 3.05


107361072513 Hs.159486 Human RPL13-2 pseudogene m8,
complete 3.05


7575 D81886 Hs.59908 ESTs 3.05


116999H84644 Hs.40707 EST 3.05


119554W38188 (NONE) 3.05


120934AA226198 gb:nc26a07.s1 NCI_CGAP-Prt
Homo Sapiens 3.05


125805AI160594 Hs.166656 ESTs, Highly similar to S49460
1 12 glutamate 3.05
~ 2


7 AA331156 gb:EST35034 Embryo, 6 week,
63 subtracted ( 3.05


128025T64877 Hs.108479 ESTs 3.05


131090A1143139 Hs.2288 visinin-like 1 3.05


112197NM 003655Hs.5637 ESTs 3.05


133492L40397 Hs.74137 transmembrane trafficking
1 1 protein 3.04
5


18485AA508515 Hs.291049 ESTs 3.pq


113893A1373741 Hs.593B4 hypothetical protein MGC3047
3.04


116911AW205577 Hs.308435 ESTs, Moderately similar to
KIAA0745 pro 3.04


132833078525 Hs.57783 eukaryotic translation initiation
factor 3.04


124724H20816 Hs.112423 Homo Sapiens m8; cD DKFZp58611420
1 (f 3.04


05894AI904740 Hs.25691 receptor (calcitonin) activity
modifying 3.04


129991828386 Hs.179925 ESTs, Weakly similar to ALUB_HUMAN
ALU S 3.04


128714T85231 Hs.179661 tubulin, beta 5 3.04


134650076376 Hs.87247 harakiri, BCL2-interacting
protein (coot 3.04


106851AI458623 gbak04g09.x1 NCI-CGAP_Lu24
25 1334 Homo Sapiens 3.04


45 AC005262 Hs.73797 guanine nucleotide binding
protein (G pr 3.04


102561AU077228 Hs.77256 enhancerofzeste(Drosophila)homolog
2 3.04


127542AA703684 Hs.245474 ESTs, Moderately similar to
ALUS-HUMAN A 3.03


113043AI628789 Hs.7483 ESTs 3.03


134710A1433797 Ns.8889 serine hydroxymethyltransferase
30 11 1 (solub 3.03


9245 AI815733 Hs.114360 transforming growth factor
beta-stimulat 3.03


106391AW959538 Hs.321214 hypothetical protein DKFZp564D0478
3.03


114607AF041260 Hs.129057 breast carcinoma amplified
sequence 1 3.03


116083AA455706 Hs.44581 heat shock protein hsp70-related
protein 3.03


132079AI701457 Hs.38694 ESTs 3
03


35 103825A1571835 Hs.55468 .
ESTs 3.03


106438AI141031 Hs.21342 ESTs 3.03


124359N22508 Hs.139315 Homo Sapiens cD: FLJ21479
fis, clone C 3.03


126384AW090198 Hs.4779 KIAA1150 protein 3.03


127995AA970953 Hs.128709 ESTs 3.03
4~ 1279
1


8 AA837029 Hs.157463 ESTs 3.02


124417N34059 gb:yv28h09.s1 Snares fetal
liver spleen 3.02


124357N22401 gb:yw37g07.s1 Morton Fetal
Cochlea Homo 3.02


105437AF151076 Hs.25199 hypothetical protein 3.02


101158AW327723 Hs.76122 splicing factor, arginine/serine-rich
45 1 4 3.02


13897891601 Hs.4947 hypothetical protein FLJ22584
3.02


100159AA285268 Hs.23488 KIAA0107 gene product 3.02


106487A1697340 Hs.135265 Homo Sapiens clone FLB8436
PR02277 m8, 3.02


124977F04819 Hs.190452 KIAA0365 gene product 3.02


131631AA022569 Hs.29802 slit (Drosophila) homolog
50 1022 2 3.01


59 AL041219 Hs.82222 sema domain, immunoglobulin
domain (1g), 3.01


104399AL022316 Hs.301947 kraken-like 3.01


116536BE218027 Hs.89969 ESTs 3.00


125889AA351978 Hs.4943 hepatocellularcarcinoma associated
prat 3.00


102233AW163045 Hs.79334 nuclear factor, intedeukin
5 1 3 regulated 3.00
5


02628090322 Hs.27812 G protein-coupled receptor
23 3.00


112812H55977 Hs.35810 ESTs 3.00


114654AA101840 Hs.103679 ESTs 3.00


118555N68372 gb:za68c10.s1 Snares fetal-lung-NbHLI9W
3.00


120005W90105 Hs.94942 EST 3,00
60 123
6


59 AA421130 Hs.112640 EST 3.00


126134AL133033 Hs.4084 KIAA1025 protein 3,pp


126194H98755 Hs.302975 ESTs, Weakly similar to 2195
HUMAN ZINC 3.00


129778AK001676 Hs.12457 hypothetical protein FLJ10814
3.00


65 Table 3B:
Pkey: Unique Eos probeset identifier number
CAT number Gene cluster number
Accession: Genbank accession numbers
7o Pkey AT number Accession


123619371681 AA602964 AA609200
1


1244171642364 N34059 N46979
1


1172991632586 N75768 N22543
1


116845393481 AA649530 AA659316 H64973
1


75 1247481715080 834617
-1


1255961708455 825698 856582 856018
1


126257182217 N99638 AW973750 AA328271 H90994AA558020AA234435
1 N59599 894815


1262801572221 219417 H20866
1


1263191528523 D81689 D81802
1


104172273499 AA4764i8 AA393338 AA398747 AA476518
1


126426110687_1 AA125984 AA127189 AA065075 AA070377 AA100017 AA079891
AA113255 AA075168 AA082764 AA083380 N84829 AA084752


AA076512 AA085119 AA085208 AA085045


126433127143-1 AA325606 AA099517 N89423


114


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
1270921779998 1 T26985 244165


127099244301 1 AA347668 AW956810 244271 F07065 F07064 813506


1265361492061 AA156151 225109 005177


103731112052 AA070545 AA13i490 AA131373
1


Jr 127263_ AA331156 AA331157 AA331155
232161 1


126783113388 1 AA083531 AA126047 AA074915 AA148649


1189461683457 1 N92834 W25061


127520656170 -1 T51239


127532353907 AJ003429 AJ003367 AA56d825
1


I 112516_ T83909 868586
~ 1744223_1


112538504579 1 AA908813 870255


1125401605263 1 869751 870467 H69771 H80879 H80878


113248328626 1 T63857 AW971220 AA493469 T63699


11263117d6257 882040 870934
1


I 128360- F12374 T74059
1540098 1


12051425532 3 AA258335 AA258499


1278671511945-1 018530 T63953


120637200885 1 AA811804 AA809404 AA286907 AW977624


121481123001 AA41i931 AA411930
1


120934_ AA226198 AA226513 AA383773
177521 1


106566120358_1 BE298210 A1672315 AW086489 BE298417 AA455921
AA902537 BE32712d R1d963 AA085210 AW274273 A1333584
A1369742


A1039658 AI885095 AI476470 AI287650 AI885299
AI985381 AW592624 AW340136 AI266556 AA456390
AI310815 AA484951


121743274582_1 AA397636 AA421144


11d699135322 AA127386 815644 AA127404
1


25 106851_ A1458623 AA639708 AA485409 822065 AA485570
322947 1


123731genbank-AA609639AA609839


123973506369 -1 014805


11679374964_1 T77781 AW014157 D12d22 A1918246 AA452599 AA628d04
N35886 AA464593 AW301738 T77780 A1042309 A1095302
H60603


AW510576 H37814 W61360 AI373286 AI702287 AA152465
AW 169067 AW169012 AW340355 AI289311


109700genbank F09609F09609


118466genbank N66741N667d1


111273genbank-N70934N70934


118555genbank N68372N68372


111462genbank 805296
805296


3 116720- N73515
5 genbank N73515


118737382979_1 AA199686 N73861


111826genbank 835975835975


120376genbank-AA227469AA227469


120809genbank AA346495
AA346495


120839_ AA348913
genbank-AA348913


120873genbank-AA358015AA358015


115498genbanILAA291070AA291070


101045entrez J05614J05614


129969genbank N57818
N57818


45 108407_ AA0755i9
genbanILAA075519


122939genbanI~AA477141AA477141


117031genbank_H88353H88353


124298genbank H91679H91679


117099321871 1 H93699 H97976 H80036


101447enfrez_M21305M21305


124357genbank N22401N22401


1017232603_1 034304 AA355800 M69181 AA375523 AA093590 AA365595
567247 A1371761 AW351920 AW181991 H28934 W79172
AA653543


AA122005 W95572 AF086505 002448 W57668 T11988
W95465 AA425179 F05724 F12205 F06285 816384
T66222 F08515


F07288 AAi 50346 H83264 T86770 N36366 AA337253
5 H12001 H82899 H69395 H69380 N29054 N30920 T97385
5 T96819


AA463807 AL079860 T11987 AA305048 AA149133 T82813
AA029555 AA035109 AA449123 AA340297 AA724155
W05196


A1859528 AA149134 016426 016097 016587 016138
016107 AW021754 016500 N30019 855718 860552
N84522 Ai143322


AW519024 AA490700 N20675 AW296747 016068 D58331016518
AI141214 N67221 016423 016537 016094 016152
H28935


T66152 016362 AW022425 AA602899 AA694603 H22255
W74368 Ci 6356 AI129361 AI917986 AI582253 AI923898
A1038907


AW191970 AI678861 016429 016345 AI277790 842325
AI640420 A1004136 Ai277797 016100 F09836 T71212
AA152316


AW090781 A1055902 T1608d AW022915 016556 AW473979
T96820 AA476595 N75446 F02570 H69286 T89992
AA907493


T34275 AA156107 H11758 AI650288 H82900 AI474575
N66718 F04914 AA505470 AA993349 F01973 AI123277
F04729 016236


AA879148 AA029574 AA887046 808127 D57339 AA490477
AI669818 AI190995 AA035507 AL119272 AL135029
AA258725


AL079521 N40299 A1630191 N86148 AA341165 T28492
N83749 A1382123 A1065033 A1950411 A1935653 A1275551
AW027482


AW 197337 A1168323 A1336930 A1094099 A1351490
AA258563 A1634763 A1492374 AA983970 A1123565
T72559 F09890


65 AA669531 AI445824 T07180 AW084799 AA306254 860606
W28367 855928 W27995 AL044845 AA501890 N84045
T97274


N87532 AL135219 AA116056T06000 AA116057 T07181
808126


124677genbank 801073801073


110243genbank H26683H26683


101867entrez M96132M96132


101941entrez-S77583S77583


119052149538_1 810889 810888


126452209811 1 826067 827438


119263genbank-T15977T15977


112040genbank 843286843286


75 103657entrez 273677273677


119400genbanILT92767T92767


119554NOT_FOUND_enirez_W38188W38188


123130genbank_AA487200AA487200


123143genbank AAd87595AA487595


121950genbank-AAd29515AA429515


123265genbank_AA491209AA491209


114988genbank-AA251089AA251089


107794genbank_AA019255AA019255


IIS


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
123422 genbanI~AA598484 AA598484
109062 genbank-AAi6094i AA16094i
S TABLE
4A: A80U71164
GENES
UPREGULATED
IN GLIOBLASTOMA


Pkey: Unique Eos probeset identifier number


ExAccn: ExemptarAccessicn number, Genbank accession number


UnigenelD:Unigene number


Unigene Unigene gene title
Title:
1 ~


R1: Ratio of brain tumor to body atlas


R2: Rafio of brain tumor to normal brain


Pkey ExAccnUnigenelDUnigene Title Ri R2


412719AW016610Hs.i29911ESTs 117.8 3.3
1
S


428321AI699994Hs.301347ESTs 108.9 3
9


455601A1368680Hs.816SRY (sex determining 107.5 .
region Y)-box 2 9.9


431917D16181Hs,2868peripheral myelin protein99.0 11
2 8


415817088967Hs.78867protein tyrosine phosphatase,72.0 .
receptor-i 11
3


449494AW237014Hs.288650aquapodn 4 60.0 .
4 2.2


39285AL133916Hs.298998ESTs 58.2 2.2


447072D61594Hs,17279iyrosylprotein sulfoUansferase54.2 7
1 1


456759BE259150Hs.i27792delta (Drosophilarlike53.5 .
3 2.5


427343AI880044Hs.176977protein kinase C binding49.6 2
protein 2 2


425088AA663372Hs.169395Homo Sapiens cDNA FLJ1201549.5 .
~S fis, clone HE 3.1


412959D87458Hs.75090KIAA0282 protein 46.3 3
0


447004AW296968Hs.157539ESTs 43.7 .
3.2


436878BE465204Hs.47448ESTs 39.8 10
8


433551AI985544Hs,289048ESTs 39.7 .
4.3


425842AI587490Hs.i59623NK-2 (Drosophila) homolog39.3 26.2
30 4 B


07034084540 gb:Human dystrobrevin 39.1 39.1
isoform DTN-3 (DTN


431725X65724Hs.2839Nome disease (pseudoglioma)38.4 3
7


453392023752Hs.32964SRY (sex determining 37.5 .
region Y)-box 11 22
1


447197836075 gb:yh88b01.s1 Soares 37.5 ,
placenta Nb2HP Homo 13
9


439415F05538Hs.12825ESTs 35.4 .
3 3.1
S


409395046745Hs.54435dystrobrevin, alpha 34.3 3
0


449539W80363Hs.58446ESTs 33.6 .
33
6


408562A1436323Hs.31141Homo Sapiens mRNA for 32.8 .
KIAA1568 protein, 5
9


431019NM-005249Hs.2714forkhead box G18 32.4 .
17
0


427540812014Hs.20976ESTs 32.1 .
40 2.0


425057AA826434Hs.96944ESTs 31.0 2
3


431941AK000106Hs.272227Homo Sapiens cDNA FLJ2009930.8 .
fis, clone CO 30.8


416829AB013805Hs.80220catenin (cadherin-associated30.4 2
protein), d 2


420807AA280627Hs.57846ESTs 30.4 ,
30
4


444190AI878918Hs.10526cysteine and glycine-rich30.4 .
4S 4 protein 2 30.4
4


29 M85835Hs.12827ESTs 30.2 7
66 2


444471AB020684Hs.11217KIAA0877 protein 29.5 .
29.5


451678AA374181Hs.26799DKFZP564D0764 protein 28.8 3
0


439979AW600291Hs.6823hypotheficaiprotein 27,7 .
FLJ10430 3
2


433800A1034361Hs.135150lung type-I cell membrane-associated27,1 .
S~ 4 gly 27,1
4


4 AL042201Hs.21273ESTs 26.9 26
0 9
35


411078AI222020Hs.182364ESTs, Weakly similar 26.0 .
to 25 kDa trypsin 26
t 0


407808AA663559Hs.289109dimethylarginine dimethylaminohydrolase25.8 .
2
2


416155AI807264Hs.205442ESTs, Weakly similar 25.5 .
to AF1176101 inner 25
5


421659NM Hs.106511protocadherin 17 25.0 .
SS 014459 3.3


430132AA204686Hs.234149hypothetical protein 24.7 24.7
FLJ20647


433332AI367347Hs.127809ESTs 24.6 24
6


452744A1267652Hs.30504Homo Sapiens mRNA; 23.8 .
cDNA DKFZp434E082 23.8
(fr


419271N34901Hs.238532ESTs 23.6 5
5


447397BE247676Hs.18442E-1 enzyme 23.1 .
43 3.2


9039 A1656707Hs.48713ESTs 23.0 7
2


414175AI308876Hs.103849ESTs 22.2 .
2
0


451099852795Hs.25954interleukin 13 receptor,22.0 .
alpha 2 7
6


410102AW248508Hs.279727Homo Sapiens cDNA FLJ1403521.6 .
fis, clone HE 2
3


415910020350Hs.78913chemokine (GX3-C) receptor21.2 ,
6S 1 3,0


451-068AW503398Hs.2i0047ESTs 21.0 4
7


454117BEd10100Hs.40368adaptor-related protein20.8 .
complex t, sigma 20
8


443850AW014723Ns.134719ESTs 20.4 .
38
5


418738AW388633Hs.6682ESTs 20.2 .
2
2


449433A1672096Hs.9012ESTs 19.9 .
4 16.6


357D6W31254Hs.7045GL004 protein 19.7 19
7


407192AA609200 gb:af12e02.s1 Soares 19.7 .
testis-NHT Homo sap 19
7


416892L24498Hs.80409growth arrest and DNA-damage-inducible,19.6 .
19
6


442562BE379584Hs.34789ESTs 19.4 .
19
4


439451AF086270Hs.278554heterochromatin-like 19.1 .
7S 4 protein 1 17.4


26320W47595Hs.169300transforming growth 18.7 5
factor, beta 2 4


412986X81120Hs.75110cannabinoid receptorl 18.6 .
(brain) 18
6


452106A1141031Hs.21342ESTs 18.6 .
1D
3


431173AW971198Hs.294068ESTs 18.6 .
18
6


422503AA410506Hs.i H.sapiens mRNA for 18.5 .
4 18578ribosomal protein 18.5
L18


19088AI538323Hs.77496small nuclear ribonucleoprotein18.5 18
polypept 5


443547AW271273Hs.23767Homo Sapiens cDNA FLJ 18.5 .
12666 fis, clone NT 5
1


451592AI805416Hs.213897ESTs 18.4 .
18
4


450313A1038989Hs.24809hypothetical protein 18.3 .
FLJ10826 18.3


116


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422544AB018259Hs.118140KIAA0716 gene product 18.2 4.7


408096BE250162Hs.83765dihydrofotate reductase18.0 18.0


418027AB037807Hs.83293hypotheficalprolein 18.0 8.2


414117W88559Hs.1787proteolipid protein 18.0 18.0
(Pelizaeus-Meabache


429418AI381028Hs.99283ESTs 17.8 17.8


432527AW975028Hs.102754ESTs 17.7 4.2


447809AW207605Hs.164230ESTs, Highly similar 17.5 4.3
1o phosphodiesteras


419704AA429104Hs.45057ESTs 17.4 4.6


436476AA326108Hs.53631ESTs, Weakly similar 17.4 2.1
to enhancer-of-spli


1 445133AW157646Hs.153506ESTs, Weakly similar 17.3 18.8
~ to AF1507551 micro


446659AI335361Hs.226376ESTs 17.2 2.6


409049A1423132Hs.146343ESTs 17.2 3.8


443672AA323362Hs.9667butyrobelaine (gamma),17.2 11.0
2-oxoglutarate d1


407748AL079409Hs.38176KIAA0606 protein; SCN 17.0 6.3
Circadian Oscillat


1 438527AI969251Hs.143237ESTs 16.9 16.9



417791AW965339Hs.ti1471ESTs 16.8 10.5


417355D13168Hs.82002endothelin receptor 16.4 16.4
type B


427897NM Hs.181060apelin; peptide ligand16.3 4.2
017413 for APJ receptor


419721NM Hs.288650aquaporin 4 16.2 4.4
001650


427701AA411101Hs.221750ESTs 16.1 3.9


432435BE218886Hs.282070ESTs 16.1 5.7


426809BE313114Hs.29706ESTs 16.0 10.0


407881AW072003Hs.40968heparan sulfate (glucosamine}15.9 15.9
3-0-sulfot


400859 15.7 15.7


409731AA125985Hs.56145ihymosin, beta, idenfified15.6 15.6
in neuroblast


420092AA814043Hs.88045ESTs 15.6 5.4


449605AW138581Hs.198416ESTs 15.5 3.0


422365AF035537Hs.115521REV3 (yeast homology-like,15.3 4.6
catalytic sub


449611AI970394Hs.197075ESTs 15.2 15.2


30 414922D00723Hs.77631glycine cleavage system15.2 5.6
protein H (amino


405238 15.1 2.8


429007D80642 gb:HUM092E09B Human 15.0 3.5
fetal brain (TFujiwa


409638AW450420Hs.21335ESTs 14.9 7.1


445888AF070564Hs.13415Homo Sapiens clone 14.8 5.7
24571 mRNA sequence


35 416737AF154335Hs.79691LIM domain protein 14.7 4.2


429163AA884766 gb:am20a10.s1 Soares-NFLLT-GBC-S114.6 3.0
Homo s


436870AW204219Hs.43679ESTs ' 14.6 2.6


443181A1039201Hs.54548ESTs 14.6 3.5


436281AW411194Hs.120051ESTs 14.5 8.5


449448D60730Hs.57471ESTs 14.4 4.8


d22564AI148006Hs.222120ESTs 14.4 14.4


448243AW369771Hs.77496small nuclear dbonucleoprotein14.3 2.4
polypept


428748AW593206Hs.98785ESTs 1d.2 14.2


452576AB023177Hs.29900KIAA0960 protein 14.1 8.1


45 452461N78223Hs.108106transcription factor 14.1 12.8


449670F07693Hs.23869Homo Sapiens mRNA; 14.1 14.1
cDNA DKFZp434K2172
(f


436637AI783629Hs.26766ESTs 14.0 2.3


429597NM a disinlegrin and metalloproteinase13.9 13.9
003816 doma
Hs.2442


419078M93119Hs.89584insulinoma-associated 13.9 2.9
1


410889X91662Hs.66744twist (Drosophila) 13.9 4.1
homolog (acrocephalos


452355N54926Hs.29202G protein-coupled receptor3413.9 13.9


421452A1925946Hs.104530fetal hypothetical 13.9 13.9
protein


430290AI734i10Hs.i36355ESTs 13.8 13.8


430387AW372884Hs.240770nuclear cap binding 13.6 13.6
protein subunit 2,
2


55 415875AA89d876Hs.5687protein phosphatase 13.5 13.5
1B (formerly 2C),
ma


416795AI497778Hs.168053ESTs, Highly similar 13.5 13.5
to AF2279481 HBV p


422025BE348774Hs.122554ESTs 13.3 13.3


400992 13.3 5.5


413174AA723564Hs.191343ESTs 13.2 2.5


60 425187AW014486Hs.22509ESTs 13.1 8.2


456965AW131888Hs.172792ESTs, Weakly similar 13.1 2.7
to hypothetical pro


419852AW503756Hs.286184hypothefical protein 13.0 2.4
dJ551 D2.5


409327L41162Hs.53563collagen, type IX, 12.9 4.0
alpha 3


439519AA837118Hs.118366ESTs 12.9 7.6


65 436299AK000767Hs.5111hypothetical protein 12.7 3.1
FLJ20729


446657AI335191Hs.260702ESTs, Moderately similar12.6 12.6
to ALU7-HUMAN A


423073BE252922Hs.123119MAD (mothers against 12.6 12.6
decapentaplegic, Dr


424278AK000723Hs.144517hypothetical protein 12.6 12.6
FLJ20716


451996AW514021Hs.245510ESTs 12.6 7.0


70 400860 12.5 23.1


439579AF086400 gb:Homo Sapiens full 12.4 12.4
length insert cDNA


408312AF263613Hs.44198intracellular membrane-associated12.4 12.4
caiciu


419948A8041035Hs.93847NADPH oxidase 4 12.4 2.4


427304AA761526Hs.163853ESTs 12.3 12.3


75 419498AL036591Hs.20887hypothetical protein 12.2 12.2
FLJ10392


428137AA421792Hs.170999ESTs 12.2 12.2


432683AW995441Hs.10475ESTs 12.2 2.0


408622AA056060Hs.202577Homo Sapiens cDNA FLJ 12.1 12.1
12166 fis, clone MA


453884AA355925Hs.36232KIAA0186 gene product 12.0 5.2


441440AI8079B1Hs.30495ESTs 12.0 3.6


414217AI309298Hs.279898Homo Sapiens cDNA: 12.0 62.7
FLJ23165 fis, clone
L


410227A8009284Hs.61152exostoses (multiple)-like11.9 2.9
2


439444AI277652Hs.54578ESTs 11.9 16.5


117


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433309AA807060Hs.126558ESTs 11.7 9.0


439170AA332365Hs.165539ESTs 11.6 9.7


417160N76497Hs.1787proteofipid protein 11.5 7.2
(Pelizaeus-Meabache


424668D83702Hs.151573cryptochrome 1 (photolyase-like)11.5 5.8


410611AW954134Hs.20924KIAA1628 protein 11.5 28.2


437124AA554458Hs.204200ESTs 11,5 11.5


418858AW961605Hs.21145Homo Sapiens cDNA: 11.3 11.3
FLJ22489 fis, clone
H


423fi00A1633559Hs.29076Homo Sapiens cDNA: 11.3 2.8
FLJ21841 fis, clone
H


429393AA383024Hs.201603ESTs, Highly similar 11.3 11.3
to hypothetical pro


1 431103M57399Hs.44pteiotrophin (heparin 11.3 3.4
~ binding growth fat


452092BE245374Hs.27842hypotheficalprotein 11.3 11.7
FLJ11210


431701AW935490Hs.14658ESTs 11.3 2.6


429399AA452244Hs.16727ESTs 11,2 2.2


408988AL119844Hs.49476Homo Sapiens clone 11.2 27.8
TUAB Cri-du-chat regi


442671At005668Hs.134779EST 11.1 11.1


402524 11'1 11'1


415558AA885143Hs.1257i9ESTs 11.1 11.1


422390AW450893Hs.121830ESTs, Weakly similar 11.0 8.8
to KIAA0924 protein


418475AI858732Hs.30443sentrinISUMO-specific 11.0 6.1
protease


458809AW972512Hs.20985sin3-associated polypepfide,11.0 5.6
30kD


410297AA148710Hs.159441ESTs 11.0 3.3


444017004840Hs.214neuro-ontological ventral11.0 11.0
antigen 1


437814A1088192Hs.135474ESTs, Weakly similar 10.9 3.3
to DDX9-HUMAN ATP-D


427194AA399018Hs.250835ESTs 10.8 8.0


25 432060AW971364 gb:EST383453 MADE resequences,10.8 10.0
MAGL Homo


453861A1026838Hs.30120ESTs 10.8 10.8


408829NM Hs.d8384heparan sulfate (glucosamine)10.6 3.3
006042 3-0-sulfot


416913AW934714 gb:RC1-DT0001-031299-011-all10.6 3.4
DT0001 Homo


418049AA211467Hs.190488hypotheficalprotein 10.6 10.6
FLJ10120


413063AL035737Hs.75184chitinase 3-like 1 10.6 27.2
(cartilage glycoprote


425264AA353953Hs.20369ESTs, Weakly similar 10.5 2.0
to gonadotropin ind


434408A1031771Hs.132586ESTs 10.5 10.5


451697AW44977dHs.2572D8ESTs 10.5 6.2


436754A1061288Hs.133437ESTs, Moderately similar10.3 10.3
to gonadotropin


3 410298AI693821Hs.182185ESTs 10.3 2.9
S


412766BE544475Hs,54347ESTs 10.3 10.3


450689A1369275Hs.243010ESTs, Moderately similar10.3 10.3
to RTCO_HUMAN G


408331NM dual specificdy phosphatase10.3 4.5
007240 12
Hs,44229


442007AA301116Hs.142838Homo Sapiens cDNA: 10.3 10.3
FLJ23444 fis, clone
H


410386W26187Hs.3327Homo Sapiens cDNA: 10.2 2.1
FLJ22219 fis, clone
H


440684AI253123Hs.127356ESTs, Highly similar 10.1 10.1
io NEST HUMAN NESTI


420892AW975076Hs.172589nuclear phosphoprotein10.0 10.0
similar to S. cer


419594AA013051Hs.91d17topoisomerase (DNA) 9.9 15.8
II binding protein


419972AL041465Hs.294038ESTs, Moderately similar9.7 23.2
to ALU2-HUMAN A


433730AK002135Hs.3542hypotheticalprotein 9.6 6.5
FLJ11273


434851AA806164Hs.116502ESTs 9.5 6.5


436306AA805939Hs.117927ESTs 9.5 4.7


453331AI240665Hs.8895ESTs 9.2 5.8


414429851494Hs.71818ESTs 9.D 6.2


424998058515Hs.154138chitinase 3-like 2 8.9 18.1
0


446936H10207Hs.47314ESTs 8.9 3.6


410276A1554545Hs.68391ESTs 8.8 3.8


453857AL080235Hs.35861DKFZP586E1621 protein 8.8 3.8


448321NM adenomalous polyposis 8.8 2.0
005883 coli like
Hs.20912


55 414783AW069569Hs.75839zinc finger protein 8.7 3.0
6 (CMPX1)


441079AW150697Hs.107di8ESTs 8.7 2.2


437517AI927675Ns.99858ribosomal protein L7a 8.6 4.5


409062AL157488Hs.50150Homo sapiens mRNA; 8.6 12.2
cDNA DKFZp564B182
(fr


420630AL13310iHs.99508Homo Sapiens mRNA; 8.6 10.4
cDNA DKFZp4340092i
(f


409260AW242407Hs.18479ESTs 8.5 11.6


442343AA992480Hs.129874ESTs 8.4 4.6


416439AA180363Hs.118769ESTs 8.d 7.2


428054A1948688Hs.266619ESTs 8.2 9.2


421633AF121860Hs.tOfi2fi0sorfing nexin 10 8.2 2.6


6J~433285AW97594d ESTs 8.1 3.3
Hs.237396


433226AW503733 KIAA1488 protein 8.0 13.4
Hs.9414


424800AL035588Hs.153203MyoD family inhibitor 8.0 2.5


425681AB018297Hs.159i83KIAA0754 protein 7.9 4.8


445034AW293376 ESTs 7.9 3.7
Hs.160323


7~ 435020AW505076 7.6 6.4
Hs.301855
DiCteorge
syndrome
critical
region
gene
8


446985AL038704Hs,i56827 7.5 7.8
ESTs,
Weakly
similar
to
ALUi
HUMAN
ALU
S


446619AU076643 secreted phosphoprotein7.5 3.9
Hs.313 1 (osteopontin,


418522AA605038 Homo sapiens cDNA: 7.5 2.2
Hs.7149 FLJ21950 fis, clone
H


439864AI720078Hs.291997 7.A 6.9
ESTs


75 419723AL120193Hs.92614Homo Sapiens growth 7.4 3.5
differenfiation fact


447896AI436124Hs.294069 7.3 22.1
ESTs,
Weakly
similar
to
ORF2
contains
a


404210 7.3 40.8


436671AW137159 7.2 11.8
Hs.146151
ESTs


439231AW581935 7.2 2.5
Hs.141480
ESTs


8~'418030BE207573 neuromedin B 7.1 6.4
Hs.83321


459290NM inhibitor of DNA binding7.0 6.7
001546 4, dominant neg
Hs.34853


423869BEd09301 7.0 4.9
Hs.134012
Ciq-relatedfactor


414825X06370Hs.77432epidermal growth factor6.9 6.4
receptor (avian


118


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420D18056387Hs.94376proprotein convertase6.9 8.6
subfilisinlkexin
t


428600AW863261Hs.15036ESTs,HighlysimilartoAF1613581HSPC06.9 7.7


438380T06430Hs.6194chondroitin sulfate 6.9 3.1
proleoglycan BEHABIb


402604 6.8 7.0


417022NM Hs.80905Ras association (RaIGDSIAF-6)6.8 2.5
014737 domain fam


405239089281Hs.11958oxidative 3 alpha 6.8 2.9
hydroxysteroid dehydro


433577AW007080Hs.8817ESTs 6.6 2.6


434629AA789081Hs.4029glioma-amplified sequence-d16.6 13.9


413886AW958264Hs.103832ESTs, Weakly similar 6.6 2.2
to TRHY_HUMAN TRICH


1 451460AI797550Hs.209652ESTs 6.5 13.7
~


442145A1022650Hs.8117erbb2-interacting 6.5 15.6
protein ERBIN


437273AL137451Hs.120873ESTs, Highly similar 6.5 2.4
to hypothefical pro


418365AW014345Hs.16169DESTs 6.4 12.8


421684BE281591Hs.106768hypotheficalprotein 6.4 4.3
FLJ10511


1 449458A1805078Hs.208261ESTs 6.4 2.3



426413AA377823 gb:EST90805 Synovial 6.3 13.2
sarcoma Homo sapien


426423NM Hs.169833single-stranded-DNA-binding6.3 10.9
012446 protein


417709D8i434Hs.82426KIAA0247 gene product6.3 23.3


448499BE613280Hs.250655prothymosin, alpha 6.2 2.9
(gene sequence 28)


20 444860AW118683Hs.154150ESTs 6.2 19.4


432715AA247152Hs.200483ESTs, Weakly similar 6.2 12.7
to KIAA1074 protein


444864AW965446Hs.46637ESTs, Weakly similar 6.2 4.1
to cDNA EST yk289g5


407792A1077715Hs.39384putafive secretedligand6.2 3.4
homologoustof


431962AL049385Hs.272251Homo Sapiens mRNA; 6.1 2.6
cDNA DKFZp586M1418
(f


25 424232AB015982Hs.143460protein kinase C, 6.1 14.6
nu


436443AW138211Hs.128746ESTs 6.1 2.8


433647AA603367Hs.222294ESTs 6.1 15.0


449961AW265634Hs.133100ESTs 6.1 3.4


448704AW080932Hs.249247heterogeneous nuclear6.1 6.1
protein similar to


408393AW015318Hs.23165ESTs 6.1 21.6


450693AW450461Hs.203965ESTs fi.i 2.2


407846AA426202Hs.40403CbpIp300-interacfingtransacfivalor,6.0 2.4
wit


445817NM Hs.13340histone acetyltransferase6.0 10.9
003642 1


440650844692Hs.6640ESTs 6.0 2.1


417675A1808607Hs.3781similar to murine 6.0 2.4
leucine-rich repeat
pr


411083N41340Hs.68318hypotheticalprotein 6.0 3.6
FLJ20344


407910AA650274Hs.41296fibronectin leucine 6.0 6.0
rich transmembrane
p


402855 6.0 2.6


445594AW058463Hs.12940zinc-fingers and homeoboxes6.0 11.6
1


40 418791AA935633Hs.194628ESTs 5.9 6.7


409262AK000631Hs.52256hypothetical protein 5.9 2.3
FLJ20624


435677AA694142Hs.293726ESTs 5.9 11.8


430334A1824719Hs.47557ESTs 5.9 7.5


452834AI638627Hs.105685ESTs 5.9 2.6


45 427315AA179949Hs.175563Homo Sapiens mRNA; 5.8 3.1
cDNA DKFZp564N0763
(f


428250AW809208Hs.183297DKFZP566F2124 protein5.8 2.0


418506AA084248Hs.85339G protein-coupled 5.8 2.5
receptor 39


417115AW952792Hs.1066small nuclear ribonucleoprotein5.8 16.0
polypept


436758AW977167Hs.155272ESTs 5.8 3.6


446332AK001635Hs.14838hypothetical protein 5.7 5.1
FLJ10773


423943AF163570Hs.135756polymerase (DNA-directed)5.7 11.1
kappa


428180A1129767Hs.182874Homo Sapiens cDNA: 5.6 7.1
FLJ21929 fis, clone
H


424343AW956360Hs.4748ESTs,HighlysimilartoJN0902pituitary5.6 2.2


417318AW953937Hs.12891ESTs 5.6 25.0


55 423582BE000831Hs.23837Homo Sapiens cDNA 5.6 4.1
FLJ11812 fis, clone
HE


427472AA522539Hs.131250transposon-derived 5.4 3.5
Busier3transposase-I


434701AA460479Hs.4096tGAA0742 protein 5.4 21.2


430147860704Hs.234434hairy/enhancer-of-split5.3 2.7
related with YRP


411019AW993097Hs.48617Homo Sapiens cDNA 5.3 4.1
FLJ12540 fis, clone
NT


424939AK000059Hs.153881Homo sapiens NY-REN-625.3 Z.d
antigen mRNA, par


424028AF055084Hs.153692KIAA0686 protein 5.3 2.7


444534AW271626Hs.42294ESTs 5.3 2.1


426171A1128606Hs.301454ESTs 5.2 3.8


431843AA516420Hs.183526ESTs 5.2 6.2


65 438204AI589645Hs.128690ESTs 5.2 5.8


424635AA420687Hs.115455Homo Sapiens cDNA 5.2 8.4
FLJ14259 fis, clone
PL


436223AK001884Hs.23799ESTs 5.2 2.4


450649NM-001429 Human DNA sequence 5.2 15.3
Hs.297722 from clone RP1-85F18


441689AI123705Hs.106932ESTs 5.2 2.2


443392A1055821Hs.293420ESTs 5.1 3.3


416179819015Hs.79067MAD (mothers against 5.1 16.7
decapentaplegic,
Dr


452167N75238Hs.13075Homo Sapiens cDNA: 5.1 18.7
FLJ23013 fis, clone
L


4340D1AW950905Hs.3697serine (orcysteine) 5.0 2.4
proteinase inhibito


458435AI418718Hs.144121ESTs, Weakly similar 5.0 3.9
to dJ37E16.2 [H.sap


75 433586T85301 gb:yd78dO6.s1 Soaresfetalliverspleen5.0 2.8


452040AW973242Hs.293690ESTs 5.0 4.5


404029 5.0 d.3


421141AW1i7261Hs.125914ESTs 5.0 2.1


402605 4.9 4.2


435839AF249744Hs.25951Rho guanine nucleotide4.9 2.5
exchange factor (


416404AA180138Hs.107924ESTs 4.9 2.4


435615Y15065Hs.4975potassium voltage-gated4.9 7.2
channel, KOT-lik


448425A1500359Hs.233401ESTs 4.9 4.9


119


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
445773H73456Hs.13299Homo Sapiens mRNA; 4.9 2.9
cDNA DKFZp761 M0111
(f


448451AW015994 gb:Ul-H-BIOp-abh-g-09-D-ULs14.9 2.2
NCI_CGAP_S


444838AV65168DHs.208558ESTs 4.8 6.7


452438BE514230Hs.29595JM4 protein 4.8 2.7


443898AW804296Hs.9950Sec61 gamma 4.8 7.2


452776AA194540Hs.13522ESTs d.8 3.4


426108AA622037Hs.166468programmed cell death4.8 16.7
5


416774A1005169Hs.28274Homo Sapiens cDNA: 4.8 3.2
FLJ22049 fis, clone
H


427704AW971063Hs.292882ESTs 4.8 23.8


1 433568A1056872Hs.133386ESTs 4.8 12.8
~


410108AA081659Hs.191098KIAA1d79 protein 4.7 2.1


433556W56321Hs.111460Homo Sapiens cDNA: 4.7 11,2
FLJ21715 fis, clone
C


418962AA714835Hs.271863ESTs 4.7 2.2


404049 4.7 3.0


1 436222A1208737Hs.122810Homo sapiens cDNA d.7 3.3
S FLJ11489 fis, clone
HE


425234AW152225Hs.165909ESTs 4.7 3.1


426490NtvL001621Hs.170087arylhydrocarbon receptor4.7 9.1


426514BE616633Hs.301122bone morphogenefic 4.7 2.7
protein 7 (osteogenic


428722U76456Hs.190787fissue inhibitor of 4.6 6.7
metalloproteinase
4


451989AF169797Hs.27413adaptor protein containing4.6 13.4
pH domain, PT


412490AW803564Hs.288850Homo Sapiens cDNA: 4.6 18.4
FLJ22528 fis, clone
H


422488AI679968Hs.152060ESTs 4.6 7.7


428862NM Hs.2316SRY (sex-determining d.6 4.6
OD0346 region Y)-box 9 (ca


413724AA131466Hs.23767Homo Sapiens cDNA 4.5 11.9
FLJ12666 fis, clone
NT


25 442495A1184717 gb:qd6db01.x1 Snares d.5 4.5
tesfis-NHT Homo sap


403549 d.5 11.6


456209W60633Hs.297792ESTs 4.5 5.1


421181NM Hs.184585LIM domain only 2 4.5 10.6
005574 (rhombofin-like 1)


439566AF086387 gb:HomosapiensfulllengthinsertcDNAd.4 2.6


3 446329NM Hs.14805solute cartier family4.4 17.2
0 Ot3272 21 (organic anion


446488AB037782Hs.15119KIAA1361 protein 4.4 8.4


426110NM Hs.166563replication factor 4.4 2.5
002913 C (activator 1) 1
(14


427413BE547647Hs.177781superoxide dismutase 4.4 14.3
2, milochondrial


424340AA339036Hs.7033ESTs 4.4 3.9


3 421552AF026692Hs.105700secreted frizzled-related4.3 31.1
protein 4


422033AW245805Hs.110903claudin 5 (Vansmembrane4.3 6.1
protein deleted


434476AW858520Hs.271825ESTs 4.3 4.5


420582BE047878Hs.99093Homo Sapiens chromosome4.3 3.6
19, cosmid 82837


419904AA974411Hs.18672ESTs 4.3 17.1


407939W05608 gb:za85e01.r1 Snares 4.3 ~ 9.0
fetal lung_NbHLI9W


425636AW955696Hs.94842ESTs 4.3 3.2
~


426304AA374532Hs.297985ESTs 4.3 6.6


439653AW021103Hs.6631hypothefical protein 4.3 2.3
FLJ20373


424723BE409813Hs.152337protein arginine N-meihyltransferase4.3 2.5
3(h


45 426064BE387014Hs.i661d6Homer, neuronal immediate4.2 4.1
early gene, 3


409509AL036923Hs.127006ESTs 4.2 16.4


424391BE55D112Hs.t12712ESTs 4.2 3.8


425248AW957442Hs.252766ESTs 4.2 11.1


418259AA215404Hs.137289ESTs 4.2 19.3


445525BE149866Hs.14831ESTs 4.2 3.1


414821M63835Hs.77424Fc fragment of IgG, 4.2 34.8
high affinity la,
re


430935AW072916Hs.115654ESTs 4.2 3.0


442233AW967149Hs.28439ESTs, Weakly similar 4.2 2.4
to ORF2 (M.musculus


416959D28459Hs.80612ubiquitin-conjugating4.1 15.3
enzyme E2A (RAD6
h


55 437097N45312Hs.d6506ESTs 4.1 15.6


428189AA424030Hs.46627ESTs 4.1 3.6


434963AW974957Hs.288719Homo Sapiens cDNA 4.1 12.2
FLJ12142 fis, clone
MA


425500AB011541Hs.158200EGF-like-domain, mulfiple4.1 2.8
d


435177A1018174Hs.42936ESTs 4.1 2.1


418357244718Hs.301010ESTs, Highly similar 4.1 4.1
to AF159851 1 Rho
G


419086NM Hs.89591Kallmann syndrome 4.1 4.1
000216 1 sequence


436557W15573Hs.5027ESTs 4.0 2.1


425586F07396Hs.46751ESTs 4.0 2.2


423905AW579960Hs.135150lung type-I cell membrane-associated4.0 3.6
gly


437095D14661Hs.119Wilms' tumour 1-associating4.0 10.0
protein


425332AA633306Hs.127279ESTs 4.0 10.9


431556AF016028Hs.260039sarcospan(Kras oncogene-associated4.0 3.8
gene


427209H06509Hs.92423KIAA1566 protein 4.0 3.1


435468AW362803Hs.166271ESTs 4.0 2.2


416773AK000340Hs.79828hypotheficalprotein 4.0 2.6
FLJ20333


440483A12D0836Hs.150386ESTs 4.0 2.5


444821AA053564Hs.12040STE20-like kinase 4.0 10.4


433873AWi56913Hs.150478ESTs, Weakly similar 4.0 2.3
to KIAA0987 protein


420028AB014680Hs.8786carbohydrate (chondroifin3.9 2.8
6lkeratan) sul


75 446706AW807631Hs,190488hypothefical protein 3.9 3.8
FLJ10120


424530AI632083Hs.28511ESTs 3.9 2.2


446851AW007332Hs.16261Homo sapiens cDNA: 3.9 16.0
FLJ22063 fis, clone
H


424720M89907Hs.152292SWIISNF related, matrix3.9 4.5
associated, acti


409456U34962Hs.54473cardiac-specific homeo3.9 8.0
box


420439AW270041Hs.193053eukaryotic translafion3.9 7.9
initiation factor


447340AW961327Hs.280833ESTs 3.9 2.1


430887N66801Hs.260287ESTs, Weakly similar 3.9 2.5
to ALU7 HUMAN ALU
S


409361NM sine oculis homeobox 3.9 4.6
405982 (Drosophila) homolo
Hs.54416


120


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
426509M31166Hs.2050pentaxin-related gene,3.9 4.0
rapidly induced b


410079094362Hs.58589glycogenin 2 3.9 18.3


426818AA554827Hs.124841ESTs, Weakly similar 3.9 3.0
to ALUS HUMAN ALU
S


435232NM Hs.4854cycfin-dependent kinase3.8 4.D
001262 inhibitor 2C (p1


427228AA115770Hs.174051small nuclear ribonucleoprotein3.8 7.9
70kD pot


443801AW206942Hs.253594ESTs 3.8 3.4


450746D82673Hs.169921generalfranscdpfionfactorll,i,pseu3.8 2.2


443837A1984625Hs.9884spindle pole body 3.8 6.5
protein


435760AF231922Hs.213004chromosome 21 open 3.8 2.2
reading frame 62


1 426757AW205640Hs.158206ESTs 3.7 3.1
0


443101A1268936Hs.129872sperm surface protein3.7 2.4


440118AB040893Hs.6968KIAA1460 protein 3.7 3.5


410612AW502698Hs.118152ESTs 3.7 22.5


435869AF255910Hs.5d650vascular endothelial 3.7 4.2
juncfion-associated


1 433208AW002834Hs.24095ESTs 3.7 16.0



432357AA452506Hs.274412similar to yeast Upf3,3.7 2.6
variant A


413916N49813Hs.75615apclipoprotein GII 3.7 5.4


429766AA612710Hs.146140ESTs 3.7 3.2


437470. AL390147Hs.734742hypothetical protein 3.7 6.4
DKFZp547D065


438459T49300Hs.35304Homo Sapiens cDNA 3.7 10.7
FLJ13655 fis, clone
PL


420361N92054Hs.206910ESTs 3.7 18.7


408819AW163483Hs.48320DKFZP56681346 protein3.7 8.8


411960877776Hs.18103ESTs 3.7 2.3


435923BE301930Hs.5010Homo Sapiens clone 3.7 2.2
24672 mRNA sequence


25 440145AW021433Hs.250863ESTs 3.7 3.8


453740AL120295 gb:DKFZp761M067-s1 3.6 3.0
761(synonym:hamy2)


440975AW499914Hs.7579hypothetical protein 3.6 2.0
FLJ10402


443135AI376331Hs.156103ESTs 3.6 12.4


419687A1638859Hs.227699ESTs, Weakly similar 3.6 2.7
to Yhr217cp [S.cere


451029AA852097Hs.25829ras-related protein 3.6 2.9


414512AL044336Hs.6831golgi resident protein3.6 10.5
GCP60


410853H04588Hs.30469ESTs 3.6 23.9


419900AI469960Hs.i70698ESTs 3.6 3.6


429673AA884407Hs.211595protein tyrosine phosphatase,3.6 7.5
non-recept


35 428290AI932995Hs.183475Homo Sapiens done 3.6 9.6
25061 mRNA sequence


444381BE387335Hs.283713ESTs, Weakly similar 3.6 4.9
to CA54_HUMAN COLIA


442104L20971Hs.188phosphodiesterase 3.6 2.1
4B, cAMP-specific
(dun


441269AWOf5206Hs.178784ESTs 3.6 2.8


447961W32791Hs.170405ESTs 3.5 4.6


447735AA775268Hs.6127Homo sapiens cDNA: 3.5 2.1
FLJ23020 fis, clone
L


437580AA761075Hs.293567ESTs 3.5 3.5


447710A1420523Hs.161282ESTs 3.5 3.5


436446AW016809Hs.i19021ESTs 3.5 2.2


448412AI219083Hs.42532ESTs, Moderately similar3.5 4.1
to ALUS
HUMAN A


409712AA167385Hs.13583_ 3.5 3,8
ESTs


404048 3.5 3.2


440516S42303Hs.161cadherin 2, type 1, 3.5 5.1
N-cadherin (neuronal


409342AU077058Hs.54089BRCAt associated RING3.5 10.6
domain 1


456508AA502764Hs.123469ESTs, Weakly similar 3.5 3,8
to AF2088551 BM-01


42610fAL049987Hs.i66361Homo Sapiens mRNA; 3.5 32.2
cDNA DKFZp564F112
(fr


436252AI539519Hs.120969Homo Sapiens cDNA 3.5 4.6
FLJ 11562 fis, clone
HE


433854AA610649 gb:np95c03.s1 NCI-CGAP_Thyi3.5 3,5
Homo Sapiens


408495W68796Hs.237731ESTs 3.5 6,1


418801AA228366Hs.115122ESTs 3.5 5
1


55 422493AW474183Hs.233816ESTs 3.5 .
15.2


428141D50402Hs.182611solute carrier family3.5 2.4
11 (proton-coupled


414591AI888490Hs.55902ESTs 3.5 8.3


439627BE621702Hs.29076Homo Sapiens cDNA: 3.5 30.2
FLJ21841 fis, clone
H


444969AI203334Hs.160628ESTs 3.5 3
1


435370A1964074Hs.225838ESTs 3.5 .
3.0


443228W24781Hs.293798ESTs 3.4 4.6


414612BE274552Hs.76578protein inhibitor 3.4 5.0
of activated STAT3


437410AW023340Hs.14880ESTs 3.4 2.7


444172BE147740Hs.104558ESTs 3.4 12
9


65 428484AF104032Hs.184601solute carrier family3.4 .
7 (cationic amino 2.8


437860AA333063Hs.279898Homo Sapiens cDNA: 3.4 4.0
FLJ23165 fis, clone
L


428776AW016636Hs.i55647ESTs, Highly similar 3.4 2.5
to 8291441 [H.sapi


409493AA386192Hs.193482ESTs 3.4 3.4


d32559AW452948Hs.257631ESTs 3.4 6
3


451455AI937227Hs.8821liver-expressed antimicrobial3.4 .
pepfide 6.1


444153AK001610Hs.10414hypothetical protein 3.4 2.6
FLJi0748


422872BE326786Hs.187646ESTs 3.4 2.2


414761AU077228Hs.77256enhancerofzeste(Drosophila)homolog3.4 2.6
2


416131L03532Ns.79024heterogeneous nuclear3.4 9.5
ribonucleoprotein


75 408576NM H4 histone family, 3.4 3.4
003542 member G
Hs.46423


431770BE221880Hs.2685555'-3' exoribonuclease3.4 21.2
2


426030BE243933Hs.108642zinc finger protein 3.4 2.1
22 (KOX 15)


422573AW297985Hs.28777H2A histone family, 3.4 3.7
member L


436865AW880358Hs.190488hypothetical protein 3.4 7.6
FLJ10120


442091AW770493Hs,195904guanine nucleotide 3.4 2.9
binding protein (G
pr


d18699BE539639Hs.173030ESTs, Weakly similar 3.4 5.5
to ALUB HUMAN ALU
S


434577837316Hs.179769Homo Sapiens cDNA; 3.4 3.9
FLJ22487 fis, clone
H


430314AA369601Hs.239138pre-B-cellcolony-enhancingfactor3.4 18.8


121


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
447279AA325308Hs.18016Homo sapiens mRNA; 3,3 3.0
cDNA DKFZp586H0324
(f


410020T86315Hs.728ribonuclease, RNase 3.3 5.8
A family, 2 (liver,


447272NM Hs.17969KIAA0663 gene product3.3 13.4
014827


407656AW747986Hs.37443Homo sapiens mRNA; 3.3 2.3
cDNA DKFZp43482119
(f


435354AA678267Hs.117115ESTs 3,3 5.5


443884N20617Hs.226627leptin receptor 3.3 8.6


444984H15474Hs.12214Homo Sapiens clone 3.3 2.0
23716 mRNA sequence


431053540369Hs.249141Glutamatereceptorsubunit3.3 2.4


424682AW60d804Hs.i51717KIAA0437protein 3.3 13.7


1 457972AI419060Hs.47448ESTs 3.3 d.2
~


424762AL119442Hs.1836B4eukaryotic translation3.3 3.2
initiation factor


438666AW014d93Hs.126727ESTs 3.3 10.8


447796AW953622Hs.223025RAB31, member RAS 3.3 4.2
oncogene family


426751W92744Hs.22664ESTs 3.3 2.6


15 436251BE515065Hs.5092nucleolar protein 3.3 3.9
(KKEID repeat)


452688AA721140Hs.d9930ESTs, Weakly similar 3.3 4.9
fo 834087 hypotheti
~


416359AL042210Hs.16d93hypothetical protein 3.3 4.2
DKFZp762N2316


424090X99699Hs.139262XIAP associated factor-13.3 2.9


434987AW97511dHs.293273ESTs 3.3 2.2


428642Ntv>_,014899Hs.188006KIAA0878 protein 3.3 5.7


420372AW960049Hs.293660ESTs, Weakly similar 3.3 5.5
to A496f8 probable


422224NM_013982Hs.113264neuregulin 2 3.2 3.0


432482L19267Hs.275924dystrophic myotonica-containing3.2 2.7
WD repea


439963AW247529Hs.6793platelet-activating 3.2 2.0
factor acetylhydrola


25 428418AI368826Hs.30654ESTs 3.2 2.4


416728A8024597Hs.79658casein kinase 1, epsilon3.2 2.8


416224NM Hs.79088reticulocalbin 2, 3.2 2.2
002902 EF-hand calcium bindin


429803W81489Hs.223025RAB31, member RAS 3.2 4.3
oncogene family


431387Ai878854Hs.252229v-maf musculoaponeurotic3.2 2.8
fibrosarcoma (a


404171 3.2 35,8


435575AF2f Hs.dd234triggering receptor 3.2 2.6
3457 expressed on myeloid


426421AW367884Hs.169832zinc finger protein 3.2 3.8
42 (myeloid-specific


445070NM Hs.258adenosine A3 receptor3.2 7.6
000677


407047X65965 gb:H.sapiens SOD-2 3.2 82.0
gene for manganese
su


3 446006NM Hs.13530deafness, aulosomal 3.2 2.2
004403 dominanl5


430890X54232Hs.2699glypican 1 3.2 4.3


439807AA376417Hs.173501Homo Sapiens mRNA 3.2 2.3
for FLJ00008 protein,


430412AW341754Hs.189305ESTs 3.2 2.0


442807AL049274Hs.8736Homo Sapiens mRNA; 3.2 2.7
cDNA DKFZp564H203
(fr


420253AI656055Hs.96200neighbor of A-kinase 3.2 2.9
anchoring protein
9


436042AF284422Hs.119178canon-chloride cotransporter-tnterac6n3.2 4.6


423422AC005175Hs.128425NY-REN-24 antigen 3.2 4.0


413020898736 gb:yr31h09.r1Soaresfetalliverspleen3.2 4.1


452877AI250789Hs.32478ESTs 3.2 4.0


45 418113A1272141Hs.83484SRY (sex determining 3.1 9.0
region Yj-box 4


421097AI280112Hs.125232Homo Sapiens cDNA 3.1 2.0
FLJ13266 fis, clone
OV


450219AI826999Hs.224624ESTs 3.1 23.7


434256A1378817Hs.191847ESTs 3.1 3.4


421407T82331Hs.127453ESTs 3.1 3.9


451198AW964541Hs.11500Homo Sapiens cDNA: 3.1 3.9
FLJ21127 tis, clone
C


-045664AW968638Hs.237691ESTs 3.1 7.9


411089AA456454Hs.118637Homo Sapiens cDNA 3.1 6.0
FLJ13365 fis, clone
PL


458050AA834708 gb:od99d04.s1 NCI 3.1 4.4
CGAP_Ov2 Homo Sapiens


454140A8040888Hs.41793hypothetical protein 3.1 2.7
FLJ10474


55 417270AA4296i5Hs.98593Homo sapiens cDNA: 3.1 2.d
FLJ23233 fis, clone
C


427951AI826125Ns.43546ESTs 3.1 2.3


443693AI3d4782Hs.9683protein-kinase, interferon-inducible3.1 7.2
dou


413367NM_006517Hs.75317solute carrier family3.1 Z6
16 (monocarboxylic


429402AF116571Hs.201671SRY (sex detemtining 3.1 6.5
region Y)-box 13


447752M73700Hs.347lactotransferdn 3.1 19.4


408949AF789011Hs.49i63putative ribonuclease3.1 3.7
III


418039806859Hs.f93172ESTs 3.1 3.8


447343AA256641Hs.236894ESTs, Highly similar 3.1 2.2
to LRP1 HUMAN LOW-D


424441X14850Hs.147097H2A histone family, 3.1 3.2
member X


65 435163AA668884Hs.19155ESTs 3.1 2.1


428712AW085131Hs.190452KIAA0365 gene product3.i 2.7


434542AA769310Hs.61260hypothetical protein 3.1 14.3
FLJ1316d


428147AW629965Hs.234983ESTs 3.1 2.7


415825Y18024Hs.78877inosilot f,d,5-trisphosphate3.1 2.5
3-kinase B


422170AI791949Hs.112432anti-Mullerian hormone3.1 8.1


448801N57423FIs.179898HSPC055 protein 3.0 2.0


4135-028E295928Hs.75424inhibitor of DNA binding3.0 18.3
1, dominant neg


431562AI884334Hs.11637ESTs 3.0 3.9


410274AA381807Hs.61762hypoxia-inducible 3.0 3.0
protein 2


75 458962NM purine-rich element 3.0 3.0
005859 binding protein A
Hs.25180


436277888520Hs.120917ESTs 3.0 2.7


453288AW583292Hs.274412similar to yeast Upf3,3.0 3.0
variant A


447471AF039B43Hs.18676sprouty (Drosophila) 3.0 4.1
homolog 2


442554AWd67376Hs.129640ESTs 3.0 4.7


441466AW673081Hs.54828ESTs 3.0 3.0


420297AI628272Hs.88323ESTs 3.0 8.i


445101T75202Hs.12314Homo Sapiens mRNA; 3.0 18.7
cDNA DKFZp586C1019
(f


453405AI567972Hs.d9919ESTs 3.0 9.6


122


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434521NM_002267 karyophedn alpha 3 3.0 9.3
Hs.3886 (importin alpha 4)


447948AI620923Hs.46679ESTs 3.0 10.1


445756AA290690Hs.288493ESTs 3.0 3.5


413243AA769266Hs.193657ESTs 3.0 5.9


422845AA317841Hs.301838ESTs, Weakly similar 3.0 2.2
1o ALU1 HUMAN ALU
S


419409AW297631Hs.143792ESTs 3.0 2.1


446441AK001782Hs.15093hypothetical protein 3.0 2.1


427150BE616183Hs.173737ras-related C3 botulinum3.0 4.1
toxin substrate


421043BE379455Hs.89072ESTs 3.0 3.0


427239BE270447Hs.174070ubiquifin carrier protein3.0 4.1


433312AI241331Hs.131765ESTs 3.0 11.0


415102M31899Hs.77929excision repair cross-complementing3.0 6.0
rode


414702122005Hs.76932cell division cycle 3.0 3.3
34


428673AW601325Hs.274472high-mobility group 3.0 15.8
(nonhistone chromoso


422676D28481Hs.1570histamine receptor 3.0 2.1
H1


451693BF220445HS.279635ESTs 3.0 2.3


412420AL035668Hs.73853bone morphogenefic 3.0 10.5
protein 2


424005AB033041Hs.137507KIAA1215 protein 3.0 3.9


440769BE561793 gb:601346642F1 NIH 3.0 5.1
MGC_8 Homo Sapiens
cD


2~ 428832AA578229 gb:nl22b12.s1 NCI CGAP3.0 2.3
HSC1 Homo Sapiens


430293AI416988Hs.238272inositol 1,4,5-triphosphate3.0 6.3
receptor, ty


450883NM-001348Hs.25619death-associated protein3.0 5.6
kinase 3


407879AA045464Hs.6557ESTs 2,9 7.0


426167AF039023Hs.167496Homo Sapiens cDNA FLJ 2.9 2.6
11120 fis, clone PL


435281A8020699Hs.4864KIAA0892 protein 2.9 3.9


432339AW411259Hs.25945ESTs 2.9 2.9


440524871264Hs.16798ESTs 2.9 9.7


408083BE383668Hs.42484hypothetical protein 2.9 4.4
FW10618


427729A8033100Hs.300646Homo Sapiens cDNA FLJ117442.9 3.1
fis, clone HE


3 422072AB016255Hs.111138I(fAA0712 gene product2.9 2.9
Q


435904AF261655Hs.89101,2-alpha-mannosidaselC2.9 3.6


440100HE382685Hs.158549ESTs 2.9 3.6


448356AL120837Hs.20993high-glucose-regulated2.9 13.9
protein 8


428005AW302245Hs.181390casein kinase 1, gamma2.9 3.7
2


403019AA834626Hs.6fi718RAD54(S.cerevisiae)-like2.9 5.8


419175AW270037Hs.179507KIAA0779 protein 2.9 2.3


433592NM_004642Hs.3436deleted in oral cancer2.9 2.3
(mouse, homology


413922AI535895Hs.221024ESTs 2.9 2.8


428593AW207440Hs.185973degenerative spertnatocyte2.9 3.3
(homolog Droso


441789D52059Hs.7972KIAA0871 protein 2.9 2.1


459107AA811881Hs.28505ubiquitin-conjugating 2.9 2.8
enzyme E2H (homolo


448560BE613183Hs.23213ESTs 2.9 3.0


425304AA463844Hs.31339fibroblastgrowthfactorll2.9 3.3


434846AW295389Hs.119768ESTs 2.9 5.1


d08146845621Hs.81057ESTs, Moderately similar2.9 5.1
to CL3BC [R.nor


446644NM Hs.15791transmembrane 7 superfamily2.9 2.8
003272 member 1 (up


446808AA703226Hs.16193Homo sapiens mRNA; 2.9 8.5
cDNA DKFZp586B211
(fr


433017Y15067Hs.279914zinc finger protein 2.9 2.2
232


429500X78565Hs.289114hexabrachion (tenascin2.9 4.5
C cytotactin)


444706AK000398Hs.11747hypothetical protein 2.9 3.6
F1J20391


407925BE002320Hs.287864Homo Sapiens cDNA FLJ140302.9 2.1
fis, clone HE


431730AF208856Hs.268122hypotheticalprotein 2.9 2.5


4471 AB014599Hs.17411KIAA0699 protein 2.8 2.1
1
8


453496AA442103Hs.33084solute carrier family 2.8 7.4
2 (facilitated glu


425227H84455Hs.40639ESTs 2.8 2.3


456534X91195Hs.100623phospholipase C, beta 2.8 76.2
3, neighbor pseudo


421465AK001020Hs.104627Homo Sapiens cDNA FLJ101582.8 6.1
fis, clone HE


409095AW337272Hs.293656ESTs 2.8 34.0


424066299348Hs.112461ESTs 2.8 2.1


432945AL043683Hs.271357ESTs, Weakly similar 2.8 11.9
to unnamed protein


414079H19i84Hs.205230ESTs 2.8 2.1


414359M62194Hs.75929cadherin 11, type 2, 2.8 3.9
OB~adherin (osteob


438890AA827756Hs.135049ESTs 2.8 4.9


430354AA954810Hs.239784human homolog of Drosophila2.8 5.2
Scribble


458367AA068470Hs.83135p53-responsive gene 2.8 4.4
6


412014AI620650Hs.43761ESTs 2.8 4.8


428727AF078847Hs.191356general transcription 2.8 6.7
factor IIH, polype


447942F12628Hs.155470zinc finger protein 2.8 2.2
38 (KOX 25)


426432AF001601Hs.169857paraoxonase 2 2.8 3.5


439189A1951185Hs.i44630nuclear receptor subfamily2.8 2.5
2, group F, m


446756AW028485Hs.26136ESTs 2.8 4.1


432148AW504912Hs.81907ESTs, Moderately similar2.8 2.6
to ALU4-HUMAN A


405649 2.8 3.8


414473BE302693 gb:ba74c02.y1 NIH-MGC_202.8 2.4
Homo Sapiens cD


75 443839AW139834Hs.143321ESTs 2.8 2.1


448804AW512213Hs.42500ADP-ribosylafion factor-like2.8 2.7
5


426625AL133415Hs.2064vimentin 2.8 25.0


417528H473i5Hs.27519ESTs 2.8 11.6


453657W23237Hs.296162ESTs 2.8 3.2


432714Y12059Hs.278675txomodomain-containing2.8 6.7
4


441072AW275480Hs.39504ESTs 2.7 2.7


441297AW403084Hs.7766ubiquitin-conjugating 2.7 2,2
enzyme E2E 1 (homo


4438498E566066Hs.9893ASB3 protein 2.7 3.0


123


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408243Y00787Hs.624intedeukin 8 2.7 3.8


446243BE296396Hs.14512Homo Sapiens cDNA FLJ117612.7 3.3
fis, clone HE


432238AL133057Hs.274135Homo Sapiens mRNA; 2.7 3.0
cDNA DKFZp434K1815
(f


433944AL1175t8Hs.3686KIAA0978 protein 2.7 3.1


411400AA311919Hs.69851GAR1 protein 2.7 16.0


436840AW450376Hs.130803ESTs, Highly similar 2.7 4.1
to T00367 hypotheti


428281AA194554Hs.183434ATPase, H+transporfing,2.7 3.2
lysosomal (vacu


426340297989Hs.169370FYN oncogene related 2.7 2.0
to SRC, FGR, YES


408320AI725867Hs.20734ESTs 2.7 4.7


1 422363T55979Hs.115474replication factor 2.7 2.2
~ C (activator 1) 3
(38


436440A1471862Hs.19fi008Homo Sapiens cDNA FLJ117232.7 4.7
fis, clone HE


408912A8011084Hs.48924KIAA0512 gene product 2.7 2.1


419304A1271326Hs.146101ESTs 2.7 3.4


415045AA321559Hs.38270Homo Sapiens cDNA: 2.7 2.3
FLJ20984 fis, clone
C


15 441872BE567100Hs.154938hypothetical protein 2,7 2.3
MDS025


422343AI628633 gbay77d05.x1 NC1_CGAP-Kidl12.7 2.5
Homo sapien


415539AI733881Hs.72472ESTs 2.7 2.7


443623BE089782Hs.9877hypothetical protein 2.7 4.7


419881AA329340Hs.44649ESTs 2.7 3.3


2O 429155BE242291Hs.197540hypoxia-inducible factor2.7 5.5
1, alpha subuni


431319AA873350 gb:oh64h02.s1 NCI-CLAP-Kids2.7 65.9
Homo Sapiens


430219X99209Hs.235887HMT1 (hnRNP meihyltransferase,2.7 3.1
S. cerevi


421016AA504583Hs.101047transcription iactor 2.7 5.2
3 (E2A immunogtobul


417259AW903838Hs.81800chondroitin sulfate 2.7 10.7
proteogiycan 2 (vers


25 431747AW979134Hs.1070Dhypothetical protein 2.7 2.9


408085N25929Hs.d2500ADP-ribosylation factor-like2.7 7.8
5


426218AF119043Hs.168005transcriptionalintermediary2.7 4.5
faciori ga


434845BE267057Hs.4200hypotheficalprotein 2.7 4.6
R32184_1


451644N23235Hs.30567ESTs 2.7 2.3


428408W74437Hs.i88757Homo Sapiens mRNA; 2.7 5.7
cDNA DKFZp564M113
(fr


446627AI973016Hs.15725hypotheficalprotein 2.7 2.9
SBBI48


450167AA446404Hs.24563NTF2-related export 2.7 9.9
protein 1


408821AL050385Hs.48332NIMA (never in mitosis2.7 2.1
gene a)-related k


452068W76412Hs.57877ESTs 2.7 2.1


3 431129AL137751Hs.263671Homo Sapiens mRNA; 2.7 6.2
cDNA DKFZp43410812
(f


429025AI399910Hs.4842ESTs 2.7 2.9


421114AW975051Hs.293156ESTs 2.7 8.8


428755D87454Hs.192966KIAA0265 protein 2.7 3.0


416391A1878927Hs.79284mesoderm specific transcript2.7 5.7
(mouse) hom


414283AW96001tHs.154993ESTs 2.7 5.9


425262D87119Hs.155418GS3955 protein 2.7 3.7


447726AL137638Hs.19368Homo Sapiens mRNA; 2.7 14,3
cDNA DKFZp434J065
(fr


424623AW963062Hs.165809ESTs 2.7 5.6


444772AW450800Hs.176859ESTs 2.7 2.7


45 428419049436Hs.286236eukaryotic translation2.7 4.6
initiation factor


441049W88920Hs.29341hypothetical protein 2.7 4.5
FLJ22376


412758Y07818Hs.74566dihydropyrimidinase-like2.6 5.1
3


447720AL038765Hs.161304ESTs 2.6 3.2


419708AK000753Hs.92374hypothetical protein 2.6 3.0


445502AW379160Hs.12813DKFZP434J21d protein 2.6 5.0


437370AL359567Hs.161962Homo Sapiens mRNA; 2.6 2.9
cDNA DKFZp547D023
(fr


444147ABD02306Hs.10351KIAA0308 protein 2.6 6.8


433193AB040881Hs.32580Homo Sapiens cDNA FLJ131222.6 3.2
fis, clone NT


445439BE243084Hs.12719regulator of nonsense 2.6 3.9
transcripts 1


55 450309W61348Hs.4864KIAA0892protein 2.6 3.8


422092AB007883Hs.111373KIAA0423 protein 2.6 2.3


424118BE269041Hs.140452cargo selection protein2.6 5.5
(mannose 6 phosp


407618AW054922Hs.53478Homo Sapiens cDNA FLJ123662.6 2.9
fis, clone MA


446493AK001389Hs.15144hypothefical protein 2.6 3.2
DKFZp5640043


442878AI868648Hs.22315ESTs 2.6 4.7


448771BE315511Hs.296244SNARE protein 2.6 5.0


416611AA568308Hs.192789ESTs, Weakly similar 2.6 7.7
to ALU7 HUMAN ALU
S


409348AI401535Hs.146090ESTs 2.6 3.5


439349A1660898Hs.195602ESTs 2.6 3.2


65 428433AA521410Hs.41371ESTs 2.6 7.9


436565BE547674Hs.204169ESTs 2.6 3.0


438662AA223599Hs.6351cleavage and polyadenylation2.6 2.6
specific fa


429362T25833Hs.200478ubiquifin-conjugating 2.6 2.3
enzyme E2M (homolo


459035AW291109Hs.208787ESTs 2.6 2.6


451814AA847992Hs.137003ESTs 2.6 19.1


452331AA598509Hs.29117H.sapiens mRNA for 2.6 2.2
pur alpha extended
3'


438461AW075485Hs.286049phosphosedne aminotransferase2.6 2.1


424362AL137646Hs.146D01Homo sapiens mRNA; 2.6 4.9
cDNA DKFZp586F0824
(f


423699H41850Hs.131846PCAF associated factor2.6 3.7
65 alpha


75 441226BE563042Hs.118820ESTs 2.6 2.5


444940AK002148Hs.12151hypothetical protein 2.6 3.4
FLJ11286


448731AI522273Hs.42640ESTs 2.6 3.2


424250AF0733i0Hs.143648insulin receptor substrate2.6 2.5
2


433468AA832055Hs.232217ESTs, Weakly similar 2.6 3.3
to ALUt_HUMAN ALU
S


$O 419925AA159850Hs.93765lipoma HMGIC fusion 2.6 4.6
partner


441364AW450466Hs.12fi830ESTs 2.6 2.6


425922AL157466Hs.162751Homo sapiens mRNA; 2.5 2.7
cDNA DKFZp761 E2423
(f


434974AA778711Hs.4310eukaryotic translation2.5 2.5
inifiation factor


124


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408392028831Hs.44566KIAA1641 protein 2.5 25.4


432426AW973152Hs.31050ESTs 2.5 10.0


436623A1417073Hs.107265ESTs 2.5 2.1


452683A1089575Hs.9071progesterone membrane 2.5 2.6
binding protein


410582AW867197Hs.14562Homo Sapiens cDNA: 2.5 3.7
FLJ21616 fis, clone
C


441328AI982794Hs.159473ESTs 2.5 9.2


453983H94997Hs.16450ESTs 2.5 26.1


438826826709Hs.10095hypothefical protein 2.5 2.3
from EUROIMAGE 1669


427899AA829286Hs.181062serum amyloid A1 2.5 20.3


1 427820BE222494Hs.180919inhibitor of DNA binding2.5 3.5
~ 2, dominant neg


458933AI638429Hs.24763RAN binding protein 2.5 3.5
1


444871046386Hs.12102sorting nexin 3 2.5 2.3


411329AL360265Hs.69554hypothetical protein 2.5 2.9
FLJ20552


424074AI902456Hs.210761ESTs 2.5 4.0


15 438988H30039Hs.107674ESTs 2.5 2.7


412836AA121384Hs.191446ESTs 2.5 5.7


430189A1298841Hs.135133ESTs, Weakly similar 2.5 3.0
to ORF YNL3ltk [S.c


432841M93425Hs.62protein tyrosine phosphatase,2.5 13.4
non-recept


416926H03i09Ns.108920NT018 protein 2.5 2.8


451429AA525993Hs.173699ESTs, Weakly similar 2.5 3.9
to ALU1 HUMAN ALU
S


416388AI417358Hs.73677ESTs 2.5 4.2


421561245399Hs.105779protein inhibitor of 2.5 7.5
activated STAT prot


436480AJ271643Hs.87469putafive acid-sensing 2.5 2.6
ion channel


416273AW57569tHs.79123KIAA0084protein 2.5 2.6


427149H94688Hs.173737ras-related C3 botulinum2.5 2.6
toxin subsfrate


453041AI680737Hs.289068franscripfion factor 2.5 2.2
4


446899NM Hs.16426podocalyxin-like 2.5 4.7
005397


447301AW958124Hs.142442HP1-BP74 2.5 3.2


447769AW873704Hs.48764ESTs 2.5 2.4


447754AW073310Hs.163533Homo Sapiens cDNA FLJ141422.5 2.5
fis, clone MA


427087BE073913Hs.1735i5uncharacterized hypothalamus2.5 23.6
protein HTO


440903AI468079Hs.126623ESTs 2.5 2.3


432353NM Hs.274411SCAN domain-containing2.5 4.1
016558 t


408196ALD34548Hs.43627SRY (sex determining 2.5 2.5
region Y)-box 22


35 411373BE326276Hs.8861ESTs 2.5 3.9


452402AIi38530Ns.22216peroxisome proliferative2.5 2.4
activated recep


429998AI458063Hs.57841ESTs 2.5 2.6


421772224958Hs.108139zinc finger protein 2.5 3.7
212


442573H93366Hs.7567Homo sapiens cDNA: 2.5 2.1
FLJ21962 fis, clone
H


40 444677ALi Hs.9242purine-rich element 2.5 3.4
10212 binding protein B


441887AW967865Hs.92145ESTs 2.5 3.3


451031AI360187Hs.4254ESTs 2.5 d.8


432450A1990739Hs.77868ORF 2.5 2.4


415860D56051Hs.78888diazepam binding inhibitor2.5 4.8
(GAGA recepto


45 439630AA313607Hs.58633Homo Sapiens cDNA: 2.4 2.3
FLJ22145 fis, clone
H


428607AB002353Hs.186840KIAA0355 gene product 2.4 4.0


415402AA164687Hs.297889ESTs 2.4 2.5


446888AL030996Hs.16411hypothetical protein 2.4 2.2
LOC57187


439208AK000299Hs.180952dynactin p62 subunit 2.4 2.4


452900AA626794Hs.250655prothymosin,alpha(gene2.4 3.4
sequence 28)


408657AA782601Hs.173328protein phosphatase 2.4 3.6
2, regulatory subuni


439143AI359214Hs.179260ESTs 2.4 2.5


439867AA847510Hs.161292ESTs 2.4 9.3


408138AA535740Hs.301967Homo Sapiens mRNA; 2.4 5.6
cDNA DKFZp434M196
(fr


428386817298Hs.295923seven in absentia (Drosophila)2.4 4.2
homolog 1


417289D86962Hs.81875growth factor receptor-bound2.4 2.2
protein 10


405268 2.4 3.1


439734AC005D13Hs.149CAMP response element-binding2.4 3.6
protein CR


445378AV653564Hs.226946ESTs 2.4 2.4


454085D824i8Hs.29626ESTs, Weakly similar 2.4 22.0
to unknown [D.melan


427354T57896Hs.191095ESTs 2.4 3.6


452906BE207039Hs.75621serine (or cysteine) 2.4 2.2
proteinase inhibito


450065AL050107Hs.301558DKFZP58611419 protein 2.4 3.6


451091AA810932Hs.131899ESTs, Weakly similar 2.4 2.7
to coded for by C.


65 414839X63692Hs.77462DNA (cytosine-5-)-methyltransferase2.4 2.6
1


420303AA258282Hs.278436KIAA1474 protein 2.4 2.0


437068AA743643Hs.291427ESTs 2.4 2.6


417446AL118671Hs.82163monoamine oxidase B 2.4 4.4


421454AI660389Hs.286108chodonic somatomammotropin2.4 3.5
hormone 1 (p


7~ 434943AI929819Hs.320xeroderma pigmentosum,2.4 6.4
complementation g


446342BE298665Hs.14846Homo Sapiens mRNA; 2.4 3.0
cDNA DKFZp5640016
(fr


452847AKOQ0857Hs.30783hypothefical protein 2.4 2.1
FLJ20850


422506820909Hs.117816soroin 2.4 2.2


405204 2.4 4.3


75 419441AW023731Hs.274368Homo Sapiens mRNA; 2.4 11.7
cDNA DKFZp58611524
(f


442293AW292634Hs.150358ESTs 2.4 2.1


451484AV648896Hs.26461hypothetical protein 2.4 2.0


438545AB032977Hs.6298KIAA1151 protein 2.4 2.1


442724AA355525Hs.159604cysteinyl-fRNAsynthetase2.4 2.8


405517 2.4 6.6


413622808950Hs.272044ESTs, Weakly similar 2.4 3.8
to ALUf HUMAN ALU
S


445679AI343868Hs.58800Homo Sapiens cDNA FLJ124882.4 2,3
fis, clone NT


408636BE294925Hs.46680CGI-l2 protein 2.4 8,7


125


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409142AL136877Hs.50758chromosome-associated2.4 2.4
polypeptide C


422043AL133649Hs.110953Homo Sapiens mRNA; 2.4 2.1
cDNA DKFZp434A139
(fr


424687J05070Hs.151738matrix metalloproteinase2.4 2.6
9 (gelatinise B


442560AA365042Hs.228598ESTs 2.4 4.9


418126T91451Hs.86538ESTs 2.4 11.7


413313NM_002047Hs.75280glycyl-tRNA synthetase2.4 2.1


415167AA160784Hs.26410ESTs 2.4 4.4


440040BE219431Hs.300713ESTs 2.4 3.4


443595AF169312Hs.9613PPAR(gamma) angiopoiefin2.4 10.7
related protein


438977AA482026Hs.298625ESTs 2.4 2.8


452066AA772149Hs.16979ESTs 2.4 5.4


428500AI815395Hs.184641delta-6 fatty acid 2.4 2.2
desalurase


408503AW119059Hs.63163ESTs, Weakly similar 2.4 2.7
to UDP-GaINAc:polyp


433401AF039698Hs.284217serologically deftned2.4 4.8
colon cancer antig


412676NM_000165Hs.74471gapjuncfion protein, 2.4 2.2
alpha 1, 43kD (con


453753BE252983Hs.35086ubiquitin specific 2.d 2.8
protease 1


424050AA211218Hs.138381famesyltransferase, 2.4 3.9
CAAX box, alpha


440225BE295782Hs.159tumor necrosis factor2.4 76.7
receptor superfami


430512AF182294Hs.241578U6 snRNA-associated 2.4 12.3
Sm-like protein LSmB


415156X84908Hs.78060phosphorylase kinase,beta2.4 10.4


435975ALti8990Hs.41997alpha-1-Bglycoprotein2.4 7.7


429831AA564489Hs.137526ESTs 2.4 4.1


407373AA031576Hs.143812Homo Sapiens cDNA 2.4 3.3
FLJ12956 fis, clone
NT


422221AA306649 gb:EST177656 Jurkat 2.4 3.8
T-cells VI Homo sapi


451351AW058261Hs.168213ESTs, Weakly similar 2.4 3.3
to ALU1 HUMAN ALU
S


410082AA081594Hs.158311Musashi (Drosophila) 2.4 2.5
homolog 1


430304AL122071Hs.238927Homo Sapiens mRNA; 2.4 6.5
cDNA DKFZp434H1235
(f


418863AL135743Hs.25566ESTs 2.4 5.2


448414BE391820Hs.21145Homo Sapiens cDNA: 2.4 3.7
FLJ22489 fis, clone
H


428351AK001701Hs.183779Homo Sapiens cDNA 2.4 6.2
FLJ10590 fis, clone
NT


425750AL050276Hs.159456zinc finger protein 2.4 5.1
288


426295AW367283Hs.75839zinc finger protein 2.4 113.6
6 (CMPX1)


408772W88532Hs.254562ESTs 2.4 12.3


426307F24978Hs.294084ESTs 2.4 4.0


3 405203 2.4 2.5
S


453537AA036755Hs.283681ESTs 2.4 3.6


431427AK000401Hs.252748Homo Sapiens cDNA 2.4 6.2
FLJ20394 fis, clone
KA


458021AI885190Hs.156089ESTs, Weakly similar 2.4 4.3
to KSAA1339 protein


453928BE222198Hs.143851ESTs 2.4 2.6


446653AV660630Hs.87627disrupter of silencing2.3 9.7
10


441626AA281167Hs.111911ESTs 2.3 23.0


446138AW504182Hs.13999KIAA0700 protein 2.3 2.2


452568AA805634Hs.3337Uansmembrane 4 superfamily2.3 22.2
member 1


417665AW852858Hs.22862ESTs 2.3 8.0


45 420088AC006486Hs.298033Homo Sapiens cDNA: 2.3 5.1
FLJ22286 fis, clone
H


421456AW579842Hs.104557hypothetical protein 2.3 2.5
FLJ 10697


412093BE242691Hs.14947ESTs 2.3 31.4


428172U09367Hs.182828zinc finger protein 2.3 4.9
136 (clone pHZ-20)


450447AF212223Hs.25010hypotheftcalprotein 2.3 2.3
P15-2


436001AW903849Hs.173840HUEL(C4orf1)-interacfingprotein2.3 4.1


414786AI246482Hs.249989ESTs 2.3 2.1


459284AF155660Hs.34401mitochondrial solute 2.3 2.9
carrier


452701NM_005110Hs.30332giutamine-fructose-6-phosphate2.3 2.6
transamin


446320AF126245Hs.i4791acyl-Coenzyme A dehydrogenase2,3 3.9
family, me


SS 446669AW972832Hs.29468ESTs 2.3 3.8


434616D79338Hs.239720CGR4-NOT transcription2.3 3.6
complex, subunit


452135A1492175Hs.301805ESTs 2.3 2.3


408696AW958157Hs.i6542ESTs 2.3 2.8


436176AL121422Hs.184013ESTs, Nighty similar 2.3 3.2
to unnamed protein


419713AW968058Hs.92381nudix (nucleoside 2.3 17.0
diphosphate linked
mot


414197W44877Hs.55501ESTs 2.3 11.8


445270A1762154Hs.54982Homo Sapiens cDNA 2.3 4.2
FLJ14014 fis, clone
HE


412247AF022375Hs.73793vascular endothelial 2.3 5.1
growth factor


426494AL119528Hs.170098KfAA0372geneproducl 2.3 4.4


65 405687 2.3 2.2


417410AF063020Hs.82110PC4 and SFRSi interacting2.3 2.0
protein 1 ~


450747Ai064821Hs.48306ESTs, Highly similar 2.3 3.8
to EWS_HUMAN RNA-BI


433680AI805366Hs.199945ESTs 2.3 6.7


420025AF184939Hs.94392LDL induced EC protein2.3 2.4


413407AI356293Hs.75339inositol polyphosphate2.3 3.1
phosphatase-like


452908A8001451Hs.30965neuronal Shc adaptor 2.3 3.0
homolog


424414AI361002Hs,94814Homo Sapiens cDNA 2.3 2.0
FLJ12168 fis, clone
MA


435791AA243086Hs.25204chondroitin 4-0-sulfotransferase2.3 2.4
2


457635AV660976Hs.3569hypothetical protein 2.3 6.9


427985AI770170Hs.65583ESTs 2.3 2.3


445496AV654019Hs.i80402Homo Sapiens cDNA: 2.3 2.3
FLJ23506 fis, clone
L


410310J02931Hs.62192coagulation factor 2.3 4.1
III (thromboplastin,


450368AU077158Hs.24930tubulin-specific chaperone2.3 3.5
a


444614844284Hs.2730heterogeneous nuclear2.3 2.6
ri6onucleoprotein


448607AL042506Hs.21599Homo Sapiens cDNA 2.3 2.8
FLJ10107 fis, clone
HE


447975BE378418Hs.127240ESTs 2.3 2.2


429767AW793022Hs.218329hypoiheficalprotein 2.3 11.5


408877AA479033Hs.130315ESTs 2.3 2.3


126


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
448481W15284Hs.74832ESTs 2.3 3.3


452833BE559681Hs.30736KIAA0124 protein 2,3 2,g


421057T58283Hs.42679ESTs 2.3 11.0


408885C02741Ns.48712hypotheticalprotein 3 4
FLJ20736 2 6


427615BE410107Hs.179817CGI-82 protein . .
2.3 2,3


448661AL049951Hs.22370Homo Sapiens mRNA; 2.3 6.3
cDNA DKFZp56400122
(f


430154AW583058Hs.234726serine (or cysteine) 2.3 34.6
proteinase inhibito


428494AA233439Hs.184634hypotheticalprotein 2.3 10.2
FLJ20005


422987AW407887Hs.301772serine/threonine kinase2 3
11 (Peutz-Jegher 3 2


408216AA741038Hs.6670ESTs . .
2.3 3.3


407862BE548267Hs.50724Homo Sapiens cDNA FLJi09342.3 5.7
fis, clone OV


432215AU076609Hs.2934ribonucleotide reductase2.3 2.1
M1 polypeptide


410086AI268405Hs.13467Homo Sapiens BAC clone2.3 2,2
RPt 1-121A8 from 7


444853AW576245Hs.149740Homo Sapiens mRNA for 2 4
FLJ00028 protein 3 5


413284AU077055Hs.289107, . ,
baculoviral IAP repeat-containing2.3 4,8
2


445547D86181Hs.273galactosytceramidase 2.3 2.5
(Krabbe disease)


420258AA477514Hs.96247franslin-associated 2.3 3,5
factor X


437223C15105Hs.107884ESTs 2,3 2,7


437353AA749195Hs.143746ESTs 3 2
2 6


426224BE085860Hs.168075karyophedn (importin) . .
beta 2 2.3 36,1


402575223024Hs.138860Rho GTPase activating 2.3 3,1
protein 1


430712AW044647Hs.196284ESTs 2.3 2,4


452036NM Hs.2762isema domain, seven 2.3 2.4
003966 thrombospondin repeat.


425180000115Hs.155024B-cell CLUlymphoma 2.3 4.3
6 (zinc finger prote


441648H05734Hs.30559ESTs 2.3 2,1


424130AL050136Hs.140945Homo Sapiens mRNA; 2.3 2.9
cDNA DKFZp586L141
(fr


414682AL021154Hs.76884inhibitor of DNA binding2.3 12.2
3, dominant neg


423814AF105020Hs.132989putative protein 0-mannosyltransferase2.3 3.7


421641AI638184Hs.106334Homo Sapiens clone 2.3 2.3
42 23836 mRNA sequence
8


7 AA640987Hs.193767ESTs 2.3 10.2
82


442159AW163390Hs.8123chromobox homolog 3 2.3 4.4
(Drosophila HP1 gamm


412541BE009398Hs.74002nuclearreceptorcoacGvatorl2.3 2.4


447217BE465754Hs.17778neuropilin 2 2.3 3.0


452336AA960961Hs.29147hypothetical protein 3 4
FLJ11015 2 1


423913NM_Oi6436Hs.301055hepatocellularcaroinoma-associatedanG. ,
2.3 3.4


411737AW160339Hs.71791hypothetical protein 2.2 2,0


412276BE262621Hs.73798macrophage migration 2.2 2.d
inhibitory factor
(


456974M12529Hs.169401apolipoprolein E 2,2 2,6


416033NM Hs.78979Golgi apparatus protein2 10
012201 1 2 4


406739AI566709Hs.182426ribosomal protein S2 . .
2.2 115.3


448646AU077149Hs.21704transcription factor 2.2 4,2
12 (HTF4, helix-loo


437371AK000868Hs.5570hypothetical protein 2.2 3,6
FLJ10006


451413AA448974Hs.26367PC3-96 protein 2.2 6.2


408665T88845Hs.112200ESTs, Weakly similar 2.2 3,2
to ALU7_HUMAN ALU
S


437548AI701596Ns.121592ESTs 2.2 3,0


452053A1750575Hs.173933nuclearfactorllA 2.2 3.3


428303AW974476Hs.183601regulator of G-protein2.2 3,4
signalling 16


441376H94227Hs.6592ESTs, Weakly similar 2,2 2,5
to salivary proline


413399BE091833 gb:IL2-BT0731-260400-076-F042.2 2.1
BT0731 Homo


448913AA194422Hs.22564myosin Vl 2.2 2.4


439053BE244588Hs.6456chaperonin containing 2.2 3,1
TCP1, subunit 2 (b


428065AI634046Hs.157313ESTs 2.2 3.5


425846AA102i74Hs.159629myosinIXB 2,2 7,1


426404AA377607Hs.273138ESTs 2 3
2 3


423464NM Hs.128856CSR1 protein . ,
016240 2,2 2,1


436135D85390Hs.5057carboxypeptidase D 2.2 9.1


450476AL045285Hs.246849ESTs, Moderately similar2.2 2,5
to ALU6_HUMAN A


420798W93774Hs.99936keratin 10 (epidermolytic2.2 2.9
hyperkeratosis


433530BE349534Hs.281789ESTs 2 2
2 1


436297A1084582Hs.5105hypothetical protein . ,
FLJ10569 2.2 2.4


433058H86865Hs.280666Homo Sapiens chromosome2.2 2.3
19, cosmid 83218


435924AW029203Hs.191952ESTs 2.2 3.2


417125AW181998Hs.81248CUG friplet repeat, 2.2 '
RNA-binding protein 2.3


449338H73444Hs.394adrenomedullin 2,2 18.3



446065AA085191Hs.6949ESTs, Weakly similar 2.2 3.1
to T2D3_HUMAN TRANS


410668BE379794Hs.65403hypothetical protein 2.2 2,5


424992AW290893Hs.96918Homo Sapiens cDNA: 2.2 10.8
FLJ2i561 fis, clone
C


437801AA613866Hs.5848Homo sapiens mRNA; 2.2 2.5
cDNA DKFZp564L222
(fr


412491W31589Hs.73957RABSA, member RAS oncogene2.2 2,4
446 family


392 AF142419Hs.15020homolog of mouse quaking2.2 3.4
01(I (KH domain


45050383591 Hs.25042Homo Sapiens mRNA full2.2 2,8
T length insert cDN


432476T94344 gb:ye31h10.s1 Stratagenelung(937210)2.2 2.6
H


424251AA677466Hs.143696coactivator-associated2.2 5.0
arginine methyltr


456619AV647917Hs.107153inhibitor of growth 2 2
family, member 1-lik 2 6


433411AI658666Hs.49994ESTs . .
2,2 2,1


424714A111d630Hs.208334Homo Sapiens cDNA: 2.2 2.7
FLJ2187d fis, clone
N


416326AF186780Hs.79219RaIGDS-like gene; KIAA09592.2 2.2
protein


407696AI697340Hs.76549ATPase, Na+IK+transporting,2.2 6.5
alpha 1 pol


445939BE018658Hs.141003Homo Sapiens cDNA: 2.2 4.4
FLJ21691 tis, clone
C


414765X07854Hs.77269guanine nucleotide 2.2 6.2
binding protein (G
pr


407136T64896Hs.287420Homo Sapiens cDNA FLJ115332.2 2.8
fis, clone HE '


453665AA626250Hs.181165eukaryotic translation2.2 2.3
elongation factor


433608AW340005Hs.164485ESTs 2.2 2,1


127


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
447646BE619752Hs.66053ESTs, Weakly similar 2.2 4.1
to S22126 finger pr


433139AB029826Hs.476493-methylcrotonyl-CoA 2.2 11.7
carboxylase biofin-


413433NM Hs.289068Uanscdptionfactor4 2.2 2.2
003199


421535AB002359Hs.105478phosphoribosylformylglycinamidine2.2 2.2
synths


428591BE313029Hs.185807Homo Sapiens clone 2.2 4.8
24758 mRNA sequence


417248AA329449Hs.247302twisted gasUulafion 2.2 2.5


403966 2.2 5.2


437112AA744692Hs.166539ESTs 2.2 3.0


414799AI752416Hs.77326insulin-like growth 2.2 4.9
factor binding prote


1 431049AA846576Hs.103267hypothetical protein 2.2 4.4
~ FLJ22548 similar to


422100Ai096988Hs.111554ADP-ribosylafion factor-like2.2 2.5
7


426543AV650198Hs.170311heterogeneous nuclear 2.2 2.4
ribonucleoprolein


423720AL044191Hs.23388Homo Sapiens cDNA: 2.2 4.2
FLJ21310 fis, clone
C


443804AL135352Hs.255883ESTs 2.2 2.2


1 435080AI831760Hs.155111ESTs 2.2 2.5



452808AF244135Hs.30670hepatocellular carcinoma-associated2.2 7.1
anti


433934AW273261Hs.216292ESTs 2.2 2.1


432004BE018302Hs.2894placentalgrowthfactor,vascularendoth2.2 4.4


452518AA280722Hs.24758ESTs 2 3
2 0


20 409600AJ011679Hs.55099Homo Sapiens mRNA; . .
cDNA DKFZp586D2123 2.2 2.3
(f


448965AF092134Hs.22679CGI-24 protein 2.2 4.0


444954AW247076Hs.12163eukaryofic translation2.2 5.3
inifiation factor


458894AW292171Hs.23978scaffold attachment 2.2 2.5
factor B


402269 2,2 2
2


25 423798AF047033Hs.301617Homo Sapiens mRNA full2.2 .
length insert cDN 4.0


413836W92003Hs.70614ESTs 2.2 3.6


432231AA339977Hs.274127CLST 11240 protein 2.1 2.1


412204A1125507Hs.130829ESTs 2.1 3.0


4388D7AA848011Hs.124570ESTs, Weakly similar 2.1 2.2
to reverse Uanscri


404170 2.1 41.6


434858AW979012Hs.13d462ESTs 2.1 2,2


426982AA149707Hs.173091ubiquitin-like 3 2.1 2.1


421939BE169531Hs.109727TAKt-binding protein 2.1 26.5
2; KIAA0733 protein


442432BE093589Hs.38178Homo Sapiens cDNA: 2.1 3.7
FLJ23468 fis, clone
H


35 424950AA602917Hs.156974ESTs 2.1 19.9


418123AA669830Hs.83530hypotheficalprotein 2.1 4.6


440467AK001519Hs.7194CGI-74 protein 2.1 5.3


437092AA744292Hs.181244major histocompatibility2.1 3.0
complex, class


421579NM Hs.105927stem cell growth factor,2.1 3.3
002975 lymphocyte secr


428953AA306610Hs.194676DKFZP434C013 protein 2.1 5.0


457313AF047002Hs.241520Uanscriptionalcoacfivator2.1 3.5


420570A1453665Hs.290870ESTs, Weakly similar 2.1 2.1
to 523650 retroviru


446918AL135125Hs.13913KIAAi577 protein 2.1 2.3


427567N24236Hs.179662nucteosome assembly 2.1 2.8
protein 1-like 1


45 446363AL117440Hs.301967Homo Sapiens mRNA; 2.1 4.0
cDNA DKFZp434M196
(fr


428482AI290352Hs.184592KIAA03d4 gene product 2.1 2.8


456559A1336273Hs.102548glucocorficoid rocepior2.1 2.3
DNA binding fact


442819BE622721Hs.301766ESTs, Weakly similar 2.1 27,1
to hypothefical pro


428808AA436007Hs.188780ESTs 2.1 5
0


414893AA215295Hs.77578ubiquifin specific 2.1 .
protease 9, X chromos 15.9


447023AA356764Hs.17i09integral membrane protein2.1 3.0
2A


402250AV655272Hs.20252novel Ras family protein2.1 4.2


429952AF080158Hs.226573inhibitor of kappa 2,1 7.9
light polypeptide
gen


420006H14429Hs.94300serologically defined 2.1 5.6
colon cancer antig


55 407316AA031663Hs.28802centaurin-alpha 2 protein2.1 4.4


417139M69043Hs.81328nuclear factor of kappa2.1 103.2
light polypeptid


414774X02419Hs.77274plasminogen activator,2.1 29.9
urokinase


430488D19589Hs.4220ESTs, Moderately similar2.1 2.1
to tetracycline


428680U69199Hs.90259ESTs, Weakly similar 2.1 2.5
to alpha 1 [H.sapie


448501AA332316Hs.4273hypothetical protein 2.1 2.0
FLJ13159


422552N39729Hs.118243deoxyribonuclease II, 2.1 2.9
lysosomal


419476AW953030Hs.59425Homo Sapiens cDNA: 2.1 3.1
FLJ23323 fis, clone
H


408681AW953853Hs.292833ESTs 2.1 3.9


417353AA375752Hs.76362general Uanscription 2.1 4.1
factor IIA, 2 (12k


65 422070AF149785Hs.111126pituitary tumor-transforming2.1 4.9
1 interacti


442711AF151073Hs.8645hypothelicalprotein 2,1 2.2


450139AK001838Hs.296323Homo Sapiens cDNA FLJ109762.1 7.4
fis, clone PL


452897BE066058Hs.269233ESTs 2.1 4.2


409147A1889208Hs.17283hypothetical protein 2.1 d.5
FLJ10890


433028AI199144Hs.283737AD-017 protein 2.1 2.6


407831BE613377Hs.15580Homo Sapiens cDNA: 2.1 8.5
FLJ22276 fis, clone
H


417871AA521368Hs.24252ESTs 2.1 2.9


428754A1521102Hs.301374ESTs, Moderately similar2.1 5.3
to ALU5_HUMAN A


430127AA2i9498Hs.233952proteasome (prosome, 2.1 4.3
macropain) subunit,


75 442622NM Hs.8546Notch (Orosophila) 2.1 8.5
000435 homolog 3


414242AA749230Hs.22666ESTs 2.1 2.8


433323AA805132Hs.30701ESTs 2.1 5.0


439022AA356599Hs.173904ESTs 2.1 6.4


443357AW016773Hs.75615apolipoprotein GII 2,1 2
0


449103T24968Hs.23038HSPC071 protein 2,1 ,
2,7


427512AB018322Hs.179507KIAA0779 protein 2.1 20


426728NM Hs.171957Uiple functional domain2.1 2.9
007118 (PTPRF interact


440112AA099014Hs.231029ESTs 2.1 2.3


1


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
446920BE397649Hs.31257Homo Sapiens cDNA FLJ136342.1 4.8
fis, clone PL


428459D44650Hs.184411gene with multiple 2.1 2.9
splice variants near


432842AW674093Hs.279525hypothetical protein 2.1 2.3
PR02605


438829AA826926Hs.204214ESTs 2 2
1 7


411442N25956Hs.101810Homo Sapiens cDNA FLJ14232. .
fis, clone NT 2.1 2.2


409423AI969783Hs.43071ESTs, Weakly similar 2.1 2.2
tc AF1519001 CGI-1


456804AI421645Hs.139851caveolin 2 2.1 15.2


434536H14486Hs.3903Cdc42 effector protein2.1 2.8
d; binder of Rho


447126AW150632Hs.62954ferrifin, heavy polypepfide2.1 25.0
1


1 442328AI952430Hs.265237ESTs 2.1 2.1
~


444488AW192879Hs.184796ESTs, Weakly similar 2.1 2.9
to PET2_HUMAN OLIGO


438874H02780 gb:yj41a1 1.r1 Scares 2.1 10.6
placenta Nb2HP Homo


412805AW954569Hs.296287ESTs 2.1 4.6


446334052427Hs.14839polymerase (RNA) II 2.1 2.3
(DNA directed) polyp


1 427201AB037860Hs.173933nuclearfactorllA 2.1 5.1



436997AA741151Hs.137323ESTs 2.1 3.0


426369AF134157Hs.169487Kreisler (mouse) maf 2.1 2.3
related leucine zip


453613F06838Hs.14763ESTs .2.1 2,4


413276224725Hs.75260mitogen inducible 2 2.1 5.5


422050AA302741Hs.25786ESTs 2.1 4.0


424797AA622394Hs.153177ribosomal protein 828 2.1 2.1


437365AW965771Hs.91065hypothetical protein 2.1 3.0
DKFZp76182423


412482AI499930Hs.181043KIAA0788 protein 2.1 2.7


418662A1801098Hs.151500ESTs 2.1 2
1


25 404030 2.1 .
2.1


437802A1475995Hs.122910ESTs 2.1 3.8


441130A1160734Hs.283429SMC (mouse) homolog, 2.1 3.5
X chromosome


416084L16991Hs.79006deoxythymidylate kinase2.1 7.4
(thymidylate kin


409944BE297925Hs.57687four and a half LIM 2.1 6.3
domains 3


425421L11669Hs.157145tetracycline transporter-like2.1 7.1
protein


428399NM Hs.184167splicing factor, arginine/serine-rich2.1 2.7
006276 7


421313NM Hs.103329KIAA0970 protein 2.1 2.6
014923


445229BE276013Hs.172364Homo Sapiens mRNA for 2.1 4.7
FLJ00086 protein,


401001 2.1 14
7


3 425159NM Hs.154868carbamoyl-phosphate 2.1 ,
5 004341 synthetase 2, aspart 7.2


438855AW946276Hs.6441tissue inhibitor of 2.1 4.9
metalloproteinase
2


433369249254Hs.3254mitochondrial ribosomal2.1 25.0
protein L23


433228F28212Hs.284247KIAA1491 protein 2.1 5.1


445392AA057478Hs.23272ESTs 2 2
0 3


433891AA613792 gb:no97h03.s1 NCI CGAP. .
Pr2 Homo Sapiens 2.0 2.5


432572AI660840Hs.191202ESTs, Weakly similar 2.0 2.9
to ALUE HUMAN !!!!


448474AI792014Hs.13809ESTs 2.0 12.1


427045H86504Hs.173328protein phosphatase 2.0 2.9
2, regulatory subuni


444916AB028956Hs.12144KIAA1033 protein 2.0 4.2


45 439177AW820275Hs.76611ESTs 2.0 3.3


423533NM Hs.129751interleukin 17 receptor2.0 5.0
014339


430057AW450303Hs.2534bone morphogenefic 2.0 2.3
protein receptor,
typ


424429063830Hs.146847TRAF family member-associated2.0 12.7
NFKB acfiv


428385AF112213Hs.184062putafive RabS-interacfing2.0 4.6
protein


50 458946AA009716Hs.42311ESTs 2.0 16.4


444816248633Hs.283742H.sapiens mRNA for 2.0 4.9
retrotransposon


426829AI761241Hs.301719ESTs 2.0 2.4


433619AW965275Hs.284288hqp0256 protein 2.0 4.4


421985AK001779Hs.110445CGI-97 protein 2.0 3.8


5 439895AB037773Hs.6762hypothetical protein 2.0 2.2
S FLJ10595


449188AW072939Hs.23200myotubularin related 2.0 2.2
protein 1


404820 2.0 2.7


425811AL039104Hs.159557karyopherin alpha 2 2.0 2.5
(RAG cohort 1, impor


422163AF027208Hs.297332Homo Sapiens cDNA: 2.0 3.7
F1J21471 fis, clone
C


431172A1125639Hs.250666hairy (Drosophila)-homolog2.0 10.2


415200AL040328Hs.301912Homo Sapiens cDNA: 2.0 2.1
FLJ22920 fis, clone
K


458176AI961519Hs.140309ESTs, Weakly similar 2.0 5.0
to KIAA0681 protein


407895844203Hs.265540HSPC042 protein 2.0 4.6


449616AI701457Hs.38694ESTs 2 2
0 0


422976AU076657Hs.1600sec61 homolog . .
2.0 5.7


430220BE378277Hs.152230ESTs 2.0 11.7


435446AA682305Hs.133268ESTs 2.0 4.2


431031AA830335Hs.105273ESTs 2.0 14.1


425233217861Hs.155218EIB~SkDa-associated 2.0 5
protein 5 6


426458D83032Hs.169984nucldar protein 2.0 .
5.9


421965AA301100 gb:EST14128 Testis 2,0 2.1
tumor Homo Sapiens
cD


427128AW301984Hs.173685Homo Sapiens cDNA FLJ126192.0 6.3
fis, clone NT


449722BE280074Hs.23960cyclin B1 2.0 2.1


450816BE271927Hs.87385ESTs 2.0 2
4


75 453507AF083217Hs.33085WD repeat domain 3 2.0 .
13,1


422801AF125672Hs.287994nuclearreceptorco-repressor22.0 3.5


418178AA043951Hs.83715Sjogren syndrome antigen2.0 3.9
B (autoanfigen


417819AI253112Hs.133540ESTs 2.0 4.0


414787AL049332Hs.77311BTG family, member 2 4
3 0 0


447032AK000310Hs.17138hypothetical protein . .
FLJ20303 2.0 7.0


431742NM_016652Hs.268281CGI-201 protein 2.0 2,5


448431BE613061Hs.300697ESTs, Weakly similar 2.0 6.5
to CA13 HUMAN COLLA


456444AA884517Hs.31856ESTs, Weakly similar 2.0 2.5
to KIAA1453 protein


129


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
419178NM Hs.89657 TATA box binding protein2.0 6.0
006284(TBP)-associate


446437AW014360Hs.202119 ESTs, Weakly similar2.0 2.2
to A46010 X-linked


449910A1074585Hs.58440 ESTs 2.0 2.1


435963AF271212Hs.87627 disrupter of silencing2
10 0 2
1


421283AI760018Hs.205071 ESTs .
.
2.0 2.6


414482557498Hs.76252 endothelin receptor 2.0 2.4
type A


450960AB013897Hs.25722 Homo sapiens mRNA 2.0 2.1
for HKR1, parfial cds


438644AI126162Hs.129037 ESTs 2.0 2.1


458343A1004775Hs.205091 ESTs Weakly similar 2
to WW domain bindin 0 6
5


412574BE410731Hs.74050 follicular lymphoma .
variant translocafio .
2.0 12.4


458079AI796870Hs.54277 ESTs 2.0 3.8


450582AI339732Hs.13144 HSPC160 protein 2.0 2.8


409936AK001691Hs.57655 hypothefical protein 2.0 3.1
FLJ10829


426865D63476Hs.172813 PAK-interacting exchange2
factor beta 0 3
3


446430AA3d6837Hs.15075 hypothefical protein .
DKFZp434E2216 .
2.0 2.0


Table
4B:


Pkey:Unique
Eos
probeset
idenfifier
number


CAT cluster number
number:
Gene


Accession:Genbank
accession
numbers


Pkey CAT Accession
Number


4471972176805-1836075 836167 AI366546


4071922200202AA602964 AA609200
1


429007_ AA443145 BF958169 AW904500
327976AL119015 D80642
1


4291631238297_1AW974271 AA592975 AA447312
AA884766


43957924302 AF086400 W73990 W79232
1


4320601235850_1AA525021 AW9.71364 AA570759


416913924456AW934714 AW749864 AW749902
1 BE162498 BE161005 BE162499
BE161006 AA190449 AW513465
BE162500 BE161007


3 426413372468AW954494 AA377823 BG219617
0 1 BG195685 BG616269 A1022688


43358632908 BC011194 AW517087 AA601054
1 T85512


4484517632 AW000978 839898 AW015994 A1598202
32 BF821479 A1521706


442495928718AI184717 AW518883 AF121173
1


43956623928 AF086387 W72711 W77884
1


35 4079396003871AW118352AW1962i5W05608


453740612139AL120295 BG291384 T88779
1


433854899720BG675161 H59558 A1699484 AA610649
1 A1937812


4130201485885_1BE048113 898736 242904


45805061684 AK057874 AW901381 AW901380
1 AV730240 T50211 AA828756 AA834708


40 44076921430 BG419454 BF924037 813764 AW793200
5 BE561793 BG698295 BE270077


428832113786681008687 AA481363 AA436432
1 81008686 AA578229 AAd81375


41447335761 BG392866 BE302693
3


422343786037AW961833 AA309282 AA551780
1 A1628633 AA551995 AW378461


431319122030BG435498 BG924768 AV718636 2
1 AA873350 T82428 T82429 AU185416
AA65844


45 422221319 BG910399 BE826714 BF905312
18 AA306649 240822 N76633


4133991511159BE091833 BE091874 BE091871
1


4324761237465_1AW973269 AA548913 T94344 AA834800
AA857492


43887452147 AF075017 866779 822463 H02780
1


433891647290AW182329 AA613792 T05304 AW858385
1


50 4219651883-13BC022394 A1742351 BE676249
AI742341 AW572776 AI566256
AI538553 81837905 AA301100
AA620903 AI142397 AW082310
A1147387 BF509145


AW968207 AA468415 AU185163
AW450843 AI568752 AW137191


TABLE
4C:


Pkey:Uniqu e number corresponding to an
Eos probeset


55 Ref: Sequence "Dunham, et al." refers
source. to the publication entitled
The "The DNA
7
digit
numbers
in
this
column
are
Genbank
Identifier
(GI)
numbers.


sequence
of
human
chromosome
22"
Dunham,
et
al.
(1999)
Nature
402:489-495.


Strand:Indicates
DNA
strand
from
which
exons
were
predicted.


Nt-position:Indicates
nucleotide
positions
of
predicted
exons.


60 Pkey Ref Strand Nt_posilion


4008599757499Minus 91888-92018,98131-98294,99474-99570


4052387249119Minus 51728-51836


4009928096828Plus 140390-140822


4008609757499Minus 151830-152104,152649-152744


65 4025249798518Minus 20529-21096


4042105006246Plus 169926-170121


4026049909420Plus 20393-20767


4028559662953Minus 59763-59909


4040297671252Plus 108716-111112


70 4026059909420Minus 47680-47973


4040493688074Minus 75765-78155


4035498081591Minus 137150-137362


4040483688074Minus 54421-56808


4041719930793Plus 173667-173783,176876-177055


75 4056494926908Minus 50032-50132,50624-50764


4052684156151Minus 24404-24521


4052047230116Plus 126569-126754


4055179454624Plus 114757-114877


4052037230116Plus 125295-125463


g0 4056876249668Minus 54787-54891,55844-55917


4039668568881Plus 158193-158277,160116-160290


4022693128156Minus 1168-1324,5492-5611,23445-23851


4041709930793Plus 168836-169248


130


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
404030 7671252 Plus 149362-151749
401001 7229886 Minus 113631-113762
404820 4678240 Plus 20475-21085
TABLE 5A: ABOU"T 43 GENES UPREGULATED IN GLIOBLASTOMA THAT ENCODE PREDICTED
MEMBRANE PROTEINS
Pkey: Unique Eos probeset identifier number
ExAccn: Fxemplar Accession number, Genbank accession number
UnigenelD: Unigene number
1 ~ Unigene Title: Unigene gene titre
R1: Ratio of brain tumor to body atlas
R2: Ratio of brain tumor to normal brain
Pkey ExAccnUnigenelDUnigene title R1 R2


15 415817088967Hs.78867protein tyrosine phosphalase,72,0 11.3
receptor-t


447072D61594Hs.17279tyrosylprotein sulfotransferase54.2 7.1
1


451099852795Hs.25954interleukin 13 receptor,22.0 7.6
alpha 2


415910020350Hs.78913chemokine (GX3-C) receptor21.2 3.0
1


412986X81120Hs.75110cannabinoid receptorl(brain)18.6 18.6


417355D13168Hs.82002endothelin receptor 16.4 16.4
type B


419721NM_001650Hs.288650aquaporin 4 16.2 4.4


452355N54926Hs.29202G protein-coupled receptor13.9 13.9
34


410227AB009284Hs.61152exostoses (multiple)-like11.9 2.9
2 ~


419723AL120193Hs.92614Homo Sapiens growth 7.4 3.5
differentiation fact


25 414825X06370Hs.77432epidermal growth factor6.9 6.4
receptor (avian


443898AW804296Hs.9950Sec61 gamma 4.8 7.2


422033AW245805Hs.110903claudin 5 (transmembrane4.3 6.1
protein deleted


414821M63835Hs.77424Fc fragment of IgG, 4.2 34.8
. high affinity la,
re


431556AF016028Hs.260039sarcospan(Kras oncogene-associated4.0 3.8
gene


3~ 435869AF255910Hs.54650vascular endothelial 3.7 4.2
junction-associated


440516S42303Hs.161cadherin 2, type 1, 3.5 5.1
N-cadherin (neuronal


428141D50402Hs.182611solute carrier family 3.5 2.4
11 (proton-coupled


428484AF104032Hs.164601solute carrier family 3.4 2.8
7 (cationic amino


431053S40369Hs.249141Glutamate receptorsubunit3.3 2.4


35 445070NM Hs.258adenosine A3 receptor 3.2 7.6
000677


430890X54232Hs.2699glypican 1 3.2 4.3


423422AC005175Hs.128425NY-REN-24 antigen 3.2 4.0


413367NM Hs.75317solute carrier family 3.1 2.6
006517 i6 (monocarboxylic


447471AF039843Hs.18676sprouty (Drosophila) 3.0 4.1
homclog 2


427150BE616183Hs.173737ras-related C3 botulinum3.0 4.1
toxin substrate


422676D28481Hs.1570histamine receptor 3.0 2.1
Hi


430293AI416988Hs.238272inositol 1,4,5-triphosphate3.0 6.3
receptor, ty


453496AA442103Hs.33084solute carrier family 2.8 7.4
2 (facilitated glu


428281AA194554Hs.183434ATPase, H+transporting,2.7 3.2
lysosomal (vacu


45 417446AL118671Hs.82163monoamine oxidase B 2.4 4.4


412676NM Hs.74471gap junction protein, 2.4 2.2
000165 alpha 1, 43kD (con


440225BE295782Hs.159tumor necrosis factor 2.4 76.7
receptor superfami


450447AF212223Hs.25010hypothetical protein 2.3 2.3
P15-2


410310J02931Hs.62192coagulation factor 2.3 4.1
III (thromboplastin,


452036NM Hs.27621sema domain, seven 2.3 2.4
003966 thrombospondin repeat


447217BE465754Hs.17778neuropilin 2 2.3 3.0


447023AA356764Hs.17109integral membrane protein2.1 3.0
2A


422070AF149785Hs.111126pituitary tumor-transforming2.1 4.9
1 interacti


456804AI421645Hs.139851caveolin 2 2.1 15.2


55 430057AW450303Hs.2534bone morphogenetic 2.0 2.3
protein receptor,
typ


422163AF027208Hs.297332Homo Sapiens cDNA: 2.0 3.7
FLJ21471 fis, clone
C


414482S57498Hs.76252endothelin receptor 2.0 2.4
type A


C)O TABLE 6A: ABOUT 397 GENES DOWNREGULATED IN GLIOBLASTOMA
Pkey: Unique Eos probeset identifier number
ExAccn: Exemplar Accession number, Genbank accession number
UnigenelD: Unigene number
Unigene Title: Unigene gene title
65 R1: Ratio of normal brain to body atlas
R2: Ratio of normal brain to brain tumor
Pkey ExAccnUnigenelDTitle R1 R2


439340A8032436Hs.6535brain-specific Na-dependent4.47 77.82
inorganic ph


7~ 424846AU077324Hs.1832neuropeptide Y 4.49 55.32


428874W32133Hs.194366transthyretin (prealbumin,7.06 45.64
amyloidosis 1


416836D54745Hs.80247cholecystokinin 9.45 44.59


401412c14p3_2958 exon 3.20 32.56


451835T63643Hs.209715ESTs, Weakly similar 3.21 28.93
to ALU7_HUMAN ALU
S


75 412768AW996044Hs.26239ESTs 3.16 28.12


415448T68645Hs.952solute carrier family 3.27 27.04
10 (sodiumlbile ac


411305BE241596Hs.69547myelin basic protein 13.80 25.92


438054AA776626Hs.62183ESTs 3.59 25.06


410837BE145698 gb:ILO-HT0205-231199-145-a073.05 24.43
HT0205 Homo


425121A1797511Hs.154679synaptotagmin 1 6.92 23.67


456763AJ271351Hs.128180B-cell translocation 3.29 23.32
gene 4


429656X05608Hs.211584neurofilament,lightpolypeptide8.03 22.56
(68kD)


451892A1821302Hs.167834ESTs 4.12 21.82


131


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
424922BE386547Hs.217112ESTs, Weakly similar 4.41 21
to Similarity to Ye 28


411666AF106564Hs.71346neurofilament3 (150kD 5.27 .
medium) 21
20


432247AA531287Hs.105805ESTs 3.25 .
21
14


436812AW298067 gb:Ul-H-BWD-ajp-g-09-0-ULs13.02 .
NCI_CGAP_Su 21.12


422234AF119818Hs.113287discs, large (Drosophila)3.38 20
homolog-associ 50


435708A1362949Hs.75169ESTs 8.79 .
20
45


423135N67655Hs.26411ESTs 6.82 .
20
28


440600AI807691Hs.126351ESTs 3.56 .
20
09


405230cNpt exon 3.31 .
l 4 7656 19.95
0


56915N55540Hs.78026ESTs, Weakly similar 3.14 19
to similar to ankyr 40


425130AA448208Hs.99163ESTs 3.53 .
19
20


416812H91010Hs.44940ESTs 3.54 .
19
08


454171AW854832 gb:OV2-CT0261-201099-011-f053.78 .
CT0261 Homo 19
04


457463AW877031Hs.272321Homo Sapiens cDNA FLJ125713.13 .
15 fis, clone NT 18.91


454589AW809699 gb:MR4-ST0124-241199-026-e124.10 18
5T0124 Homo 60


418104T05726Hs.177130ESTs 3.17 .
18
41


416357T82050Hs.268907ESTs 3.11 .
18
13


414683S78296Hs.76888internexin neuronal 5.55 .
intermediate filamen 18
13


447694AI420083Hs.170303ESTs 3.56 .
17.79


427627887582Hs.179915guanine nucleotide 4.63 17
binding protein (G 65
pr


428010AA806554Hs.185375ESTs 3.03 .
17
40


417159801761 gb:ye81f10.s1 Soaresfetalliverspleen3.23 .
17
38


436788AA766908Hs.259047ESTs 3.16 .
17
21


459349AW749381 gb:OV3-BT0381-170100-060-c023.26 .
25 4 BT0381 Homo 17.10


50214BE439763Hs.227571regulator of G-protein3.86 17
signalling 4 04


438068AI927209Hs.283089HMT1 (hnRNP methyllransferase,3.54 .
S. cerevi 16
48


437268AI754847Ns.227571regulator of G-protein5.63 .
signalling 4 16
92


435315AA700240Hs.165402ESTs 4.06 .
16
12


424240A8023i85Hs.143535calciumicalmodulin-dependent4.69 .
3 4 protein kin 15.92
~


12446AI768015Hs.92127ESTs 5.44 15
75


449714A8033015Hs.23941KIAA1189 protein 4.59 .
15
43


435832AA425688Hs.41641Bruno (Drosophila) 4.63 .
-like 4, RNA binding 14
97


437397AA349847Hs.4221hypotheticalprotein 5.93 .
DKFZp761H039 14
81


435502L13266Hs.105glutamate receptor 3.29 .
35 ionotropic N-methyl 14.61


414187BE312141 gb:601145962F1 NIH_MGC-193.37 14
Homo Sapiens c 46


417868A1078534Hs.122592ESTs 7.57 .
14
22


428536Aii43139Hs.2288visinin-like 1 5.16 .
13
98


402125c18p3-155 exon 3.11 .
13
94


440503NM Hs.7235calcium channel, voltage-dependent,3.49 .
006539 gamm 13.92


419090T85201Hs.188468ESTs 3.25 13
79


437665AA765417Hs.292053ESTs 3.07 .
13
79


457113A1734016Hs.270508ESTs 3.50 .
13
69


424933AW999974Hs.5181proliferation-associated3.59 .
2G4, 38kD 13
48


443489A1073512Hs.133916ESTs 3.24 .
45 13.20


404289c6p3-5821 exon 3.99 13
12


406534ph2_4616 exon 3.89 .
13
10


423280AA324037 gb:EST26901 Cerebellum3.38 .
II Homo Sapiens c 13
03


455421AW937661Hs.288324Homo Sapiens cDNA FLJ132833.04 .
fis, clone OV 12
93


433725AF063559Hs.283919Homo Sapiens clone 3.71 .
H00117 PR00117 mRNA, 12.85


416660898905Hs.35992ESTs 3.92 12
74


407593AW044083Hs.237008ESTs 3.85 .
12
67


451734NM Hs.26944neurogranin (protein 7.41 .
006176 kinase C substrate, 12
59


410366AI267589Hs.25214hypotheticalprotein 7.89 .
12
50


405348cNp3-13716 exon 3.45 .
12.42
Jr


442338A1761976Hs.156080ESTs 3.69 12
35


424458M29273Hs.1780myelin associated glycoprotein4.72 .
12
31


4314D0AA504607 gb:aa63a02.s1 NCI-CGAP_GCB13.42 .
Homosapiens 12
29


417754813027Hs.268703ESTs 3.35 .
12
18


440184AB002297Hs.7022dedicator of cyto-kinesis6.15 .
6O 4 3 12.11


31339AA5D6294Hs.257266ESTs 3.50 11
97


4522658E501516Hs.114772ESTs 3.82 .
11
96


419297AA446040Hs.98640Homo Sapiens cDNA: 3.16 .
FLJ21069 fis, clone 11
C 86


424991AA775471Hs.241467ESTs 3.03 .
11
64


431988AC002302Hs.77202protein kinase C, beta3.78 .
65 4 1 11.62


50987AA017202Hs.32794ESTs 3.28 11
61


440607AA894559Hs.192097ESTs 3.11 .
11
60


454566AW807605 gb:MR4-ST0098-120100-001-b063.26 .
ST0098 Homo 11
54


442000H38671Hs.8071KIAA0735 gene product;3.44 .
synaptic vesicle 11
51


437948AA772920 gb:ae73c09.s1 Stratagene3.16 .
7O schizo brain Si 11.46


401081c11p3 exon 3.18 11
921 35


438919AW979114 gb:EST391224 MAGE resequences,4.16 .
MAGP Homo 11
35


454578AW809178 gb:MR4-ST0118-261099-012-c073.02 .
ST0118 Homo 11
27


422279H69644Hs.114231Gtype lectin-like receptor-23.35 .
11
13


453101AW952776Hs.94943ESTs 3.21 .
75 11.07


455836BE145795 gb:MRO-HT0208-101299-103-a123.61 10
HT0208 Homo 83


413324V00571Hs.75294corticotropin releasing3.72 .
hormone 10
71


412266N59006Hs.26133ESTs 3.80 .
10
60


436887AW953157Hs.193235ESTs 7.24 .
10
56


454968AW849046 gb:IL3-CT0214-150300-085-H063.05 .
80 CT0214 Homo 10.53


418162T11958 gb:A802R Heart Homo 3.07 10
Sapiens cDNA clone 50
A


425537A8007913Hs.158291KIAA()444 protein 3.07 .
10
46


436230AI248723Hs.17711ESTs 3.09 .
10
45


431169AW971240 gb:EST383329 MAGE resequences,3.02 .
MALL Homo 10.43


132


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
447359NM Hs.18268adenylate kinase 5 5.91 10.40
012093


457187AA443927Hs.144360EST 3.30 10.39


407539X91103 gb:H.sapiens mRNA for 3.02 10.35
Hr44 protein.


452855817746Hs.84469ESTs 3.02 10.26


440352AI692322Hs.65373ESTs 3.03 10.20


456116228528Hs.1720046tin 3.11 10.17


458172BE007237 gb:PMO-BN0139-050500-003-g093.32 10.14
BN0139 Homo


445881AI263029Hs.210689ESTs 3.04 10.11


454059NM Hs.37048statherin 3.27 9.97
003154


1 402624clpl exon 3.05 9.94
~ 2660


441539AA937200Hs.192939ESTs 3.27 9.82


412172N76794 gb:yv45g07.r1 Soaresfetalliverspleen3.03 9.78


427942AA417856 gb:zv01d05.r1 NCI_CGAP_GCB14.09 9.73
Homo Sapiens


d3686BE0418377 ESTs 3.25 9.73
Hs.120316


15 454688AW814472 gb:MR3-ST0203-010200-109-b063.41 9.73
ST0203 Homo


446122AI362790Ns.181801ESTs 3.40 9.71


420480AL137361Hs.98173hypothe6calprotein 3.03 9.56


433447U29195Hs.3281neuronal pentraxin 3.72 9.54
II


407178AA195651Hs.104106ESTs 3.89 9.47


415614F12926Hs.165998DKFZP564M2423 protein 3.06 9.45


450518BE245175Hs.270893ESTs 3.99 9.39


d55675BE065984 gb:RC3-BT0319-120200-014-a063.46 9.32
BT0319 Homo


456459AA253074Hs.146261ESTs 4.08 9.30


423420A1571364Hs.128382Homo Sapiens mRNA; 5.18 9.23
cDNA DKFZp76111224
(f


25 455644BE064521 gb:RC4-BT0311-250200-014-d023.02 9.20
BT0311 Homo


419800AA282392Hs.191525ESTs 3.28 9.16


430964Y10929Hs.248167zincfingerprotein 186(Kruppeltype)3.04 9.00


409716AL117454Hs.56027Homo Sapiens mRNA; 3.02 9.00
cDNA DKFZp586J 1717
(f


412962AW839578Hs.18i60Homo sapiens cDNA FLJ115503.33 8.99
fis, clone HE


30 445040AW444934Hs.195929ESTs, Weakly similar 3.50 8.9G
1o pre-serum amyloi


451496AW503407 gb:Ul-HF-BNO-akw-d-11-0-ULr13.17 8.94
NIH MGC_50


424617AA344151 gb:EST50059 Gall bladder3.25 8.91
I Homo Sapiens


441914AA971496Hs.128465ESTs 3.42 8.88


405320cNp3-12168 exon 3.30 8.84


35 449179A1633785Hs.196561ESTs 3.43 8.84


400335Y13187Hs.248066Homo Sapiens dmd gene,3.13 8.78
intron 11


454962AW847645 gb:ll3-CT0213-280100-056-A044.16 8.74
CT0213 Homo


407803AW081681Hs.269064ESTs 3.09 8.73


455260AW878317 gb:MR3-OT0007-260300-206-e093.78 8.70
OT0007 Homo


431096AA324358Hs.249227Homo Sapiens DNA, cosmid4.01 8.67
clones TN62 and


424481819453Hs.1787proteolipid protein 8.12 8.63
(Pelizaeus-Merzbache


407616AW054849Hs.246831ESTs, Weakly similar 3.08 8.53
to CIKG HUMAN VOLTA


434589AF147363 gb:Homo Sapiens full 3.26 8.51
length insertcDNA


439239A1031540Hs.235331ESTs 5.78 8.48


45 410926AW810708 gb:MR2-ST0129-051099-007-g073.34 8.47
ST0129 Homo


430004U27768Hs.227571regulator of G-protein4.26 8.45
signalling 4


409623AW449185 gb:Ul-H-BI3-akg-e-05-0-ULs13.32 8.43
NCI-CGAP Su


420156AW449258Hs.6187ESTs 3.40 8.38


411555AF113537Hs.70669HMP19 protein 5.85 8.34


408509AA497035Hs.110502ESTs 3.17 8.34
0


442368A1698577Hs.202481ESTs 3.02 8.33


457870AA732217Hs.294054ESTs 3.04 8.32


437254AA831258 gb:oc73f04.s1 NCI CGAP3.35 8.24
GCB1 Homo Sapiens


415508839236 gb:yc91d03.s1 Soaresinfantbrain3.07 8.22
1N18 H


55 409483U49379Hs.54506diacylglycerol kinase,3.31 8.20
epsilon (64kD)


435229AA676556Hs.269515ESTs, Moderately similar3.21 8.19
to ALUB HUMAN !


458120W21398Hs.54523ESTs, Weakly similar 3.22 8.17
to cytochrome P-d50


444613H29627Hs.79092ESTs 3.78 8.16


41.7050N39540Ns.108029ESTs 4.06 8.14


425607U09860Hs.158333protease, serine, 7 3.68 8.06
(enterokinase)


413263BE075131 gb:PM1-BT0585-110200-003-g033.40 8.04
BT0585 Hamo


424549A1873205Hs.183114Homo Sapiens cDNA FLJ142363.27 8.03
fis, clone NT


452689F33868Hs.284176transferrin 3.03 8.01


405476cNp3_19940 exon 3.28 8.00


65 403932c5p1 exon 3.58 7.99
533


407095AF011757Hs.105937RAGE binding protein 3.32 7.96


415967H11124 gb:ym14h07.s1 Soares 3.10 7.96
infant brain 1 NIB
H


417555H65366 gb:yr67c10.r1 Soaresfetalliverspleen3.05 7.95


448985AA324885Hs.22777carbonic anhydrase 5.30 7.79
XI


70 428689NM Hs.189810sulfotransferase-related3.87 7.74
014351 protein


424140248051Hs.141308myelin oligodendrocyte4.68 7.74
glycoprotein


441099AW339393Hs.126573ESTs 3.08 7.74


448589AF017090Hs.21554KIAA1107 protein 3.10 7.73


406112ph0 exon 3.22 7.70
24243


75 458439AV647220Hs.282889ESTs, Weakly similar 3.22 7.69
to strong similarit


429859NM_007050Hs.225952protein tyrosine phosphatase,3.15 7.68
receptor t


412090AW955826Hs.12396ESTs, Weakly similar 3.01 7.67
to ALU6 HUMAN ALU
S


413547BE147440 gb:RC1-HT0229-080100-015-f093.01 7.66
HT0229 Homo


447772A1924558Hs.161399ESTs 3.04 7.63


411132AW819191 gb:CM1-ST0283-071299-061-d083.72 7.61
ST0283 Homo


425490NM_002248Hs.158173potassium intermediatelsmall3.15 7.60
conductance


454568BE141434 gb:MRO-HT0079-051099-002-d013.16 7.59
HT0079 Homo


439099AB037800Hs.6462kIAA1379 protein 3.d0 7.57


133


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415669NM Hs.78589serine (orcysteine) 5.71 7.57
005025 proteinase inhibito


428175AI81077dHs.98376ESTs 3.04 7.55


413162BE068115 gb:CMi-BT0368-061299-060-g073.43 7.54
BT0368 Homo


451361AA053854Hs.235390Homo Sapiens mRNA; 3.11 7.53
cDNA DKFZp7618101
(fr


442527AF150289Hs.205d36ESTs 3.31 7.53


450407NM Hs.24969gamma-aminobutydc acid5.24 7.53
00081 (GABA) A recepto
D


456966AI589569Hs.190082ESTs 3.13 7.47


441799AW292276Hs.127872ESTs 3.38 7.41


424185AA279752Hs.142570Homo Sapiens clone 3.16 7.40
24629 mRNA sequence


1 429783AA811987Hs.125779ESTs 3.13 7.38
~


429268AA205386Hs.198481RAR-related orphan 3.48 7.38
receptor B


400708ciipl exon 3.33 7.35
1292


402598BE314624Hs.3128polymerase (RNA) II 3.04 7.33
(DNA directed) polyp


455377AW905347 gb:OV2-NN1073-220400-159-f063.03 7.33
NN1073 Homo


1 435070AI821270Hs.116930ESTs 3.03 7.33
S


405427cNp3-17682 exon 3.03 7.25


455149AW861879 gb:CMO-CT0341-260100-160-h123.56 7.24
CT0341 Homo


402816clp3-2531 exon 3.13 7.21


422890243784Hs.787fsolute carrier family 3.40 7.15
3 25 (mitochondria)


20 422297AW961290Hs.155615ESTs 3.44 7.10


412686AW984068 gb:RCO-HN0006-160300-011-e063.91 7.09
HN0006 Homo


436383BE065178 gb:RCi-BT0314-020200-012-h013.09 7.09
BT0314 Homo


412290BE069037 gb:OV3-BT0379-161299-040-e123.04 7.08
BT0379 Homo


415486H12214Hs.13284ESTs 4.22 7.07


407728AW071502Hs.175931ESTs 3.05 7.06


448546813209Hs.21413solute carrier family 5.93 7.05
12, (potassium-chl


417275X63578Hs.818d9parvalbumin 4.08 7.04


418425A1871247Hs.6262ESTs 4.10 7.04


440558AA889574Hs.177511ESTs 3.28 7.04


3~ 411427AW846080 gb:MR3-CT0176-081099-002-b093.11 7.03
CT0176 Homo


422272AI452421Hs.77965Clk-associating RS-cyclophilin3.39 7.03


410816AW806175 gb:MRt-UM0108-130400-003-a063.30 7.02
UM0108 Homo


418375NM Hs.84389synaptosomal-associated9.93 7.01
003081 protein, 25kD


421627AI138551Hs.97318ESTs 3.10 7.01


35 447258BE047911 gbaz44a05.y1 NCI CGAP_Bm52Homosapien3.09 6.99


455547AW994078 gb:RC3-BN0036-090200-011-h023.35 6.98
BN0036 Homo


432209AW971278 gb:EST383367 MAGE resequences,3.49 6.92
MAGL Homo


404541c8p1 exon 4.62 6.89
6409


451539AA059467Hs.218933ESTs 3.01 6.88


4~ 429954A1918130Hs.21374ESTs 3.82 6.87


411138AW819500 gb:RCS-ST0293-180100-012-C073.08 6.87
ST0293 Homo


447464AW444957Hs.201897ESTs, Weakly similar 3.33 6.85
to ALU4-HUMAN ALU
S


454713AW815111 gb:OV4-ST0212-091199-023-c093.16 6.84
ST0212 Homo


415734NM Hs.78748KIAA0237 gene product 5.00 6.84
014747


45 429667AA456275Hs.44841ESTs 3.09 6.80


403008c21p3-2374 exon 3.04 6.78


446079T56522Hs.154030ESTs 3.11 6.75


441869NM Hs.8004huntingtin-associated 4.49 6.75
003947 protein interactin


437804AA828257Hs.124324ESTs 3.42 6.73


436454AA757615Hs.291509ESTs 3.01 6.72


416334H53139Hs.36271ESTs 3.12 6.70


455965BE167014 gb:CM2-HT0502-140200-088-4083.05 6.68
HT0502 Homo


445085A1569295Hs.179285ESTs 3.19 6.68


445611AW418497Hs.145583ESTs 3.61 6.68


55 437762T78028Hs.i54679synaptotagmin 1 7.21 6.68


416268H49111 gb:yo21c07.r1 5oares 3.02 6.67
adult brain N2b5H85


449766A1668690Hs.54773ESTs 3.25 6.64


443100A1033188 gb:ow94e08.s1 Soares 3.07 6.64
fetal liver-spleen


40.8070AW148852 gb:xf05d05.x1 NCI_CGAP_Bm353.12 6.60
Homo sapien


451602AW008846Hs.60857ESTs 3.05 6.59


441447AA934077Hs.126980ESTs 4.06 6.59


445078A1869975Hs.4775junctophilin 3 4.25 6.59


434501AF143878Hs.194152Homo Sapiens clone 3.25 6.58
IMAGE:115304 mRNA
seq


415960849020Hs.24974ESTs 3.34 6.58


65 403395c3p1 exon 3.59 6.57
11541


403061c2p1 exon 3.06 6.56
10450


419232A1382037Hs.87421ESTs 3.28 6.56


425984AW836277Hs.i65636hypothetical protein 6.50 6.56
DKFZp761C07121


403717c4p1_3133 exon 3.52 6.53


7~ 452178AW043576Hs.171929ESTs 3.38 6.53


455758815709Hs.284231Novel human gene mapping4.42 6.52
to chomosome 22


433858N69243Hs.192974Homo Sapiens cDNA FLJ127353.58 6.52
(is, clone NT


425440AA357518 gb:EST66256 LNCAP cells3.15 6.49
I Homo Sapiens c


419412AW161058Hs.90297synuclein, beta 5.60 6.47


75 423678AW963357Hs.7847ESTs 3.47 6.47


416625897839Hs.35758ESTs 3.10 6.46


451854T92536Hs.194096ESTs 3.28 6.46


406732AA487229Hs.2064vimentin 3.71 6.44


434619H43163Hs.32810ESTs 3.05 6.44


g0 413797BE167274Hs.5996ESTs 3.23 6.44


438612AW977980Hs.292129ESTs 3.39 6.42


412317AW991979 gb:RC1-BN0014-210100-012-f053.46 6.42
BN0014 Homo


422159N76767Hs.153406ESTs 3.03 6.41


134


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429290AF203032Hs.198760neurofilament, heavy 3.46 6.35
polypepfide (200kD)


427334844789Hs.119486ESTs, Weakly similar 3.93 6.35
to transmembrane re


453839AL138417 gb:DKFZp434B1729-r1 3.06 6.34
434(synonym:htes3)


d29096AB011106Hs.196012KIAA0534 protein 3.12 6.33


444609AW571659Hs.278081ESTs 3.30 6.33


419515S81944Hs.90791gamma-aminobutyric 3.11 6.33
acid (GABA) A recepto


418900BE207357Hs.301709ESTs 3.14 6.30


437979AA774318Hs.121708ESTs 3.25 6.29


410359838624Hs.106313ESTs 4.74 6.28


1 d15990876929Hs.29633ESTs 3.39 6.28
o


419392W28573 g6:51f10 Human retina 3.00 6.28
cDNA randomly prim


424312A8013452Hs.144931ATPase, aminophospholipid3.06 6.26
transporter (A


444762AI733700Hs.143883ESTs 3.09 6.25


447785AL041765Hs.161423ESTs 3.05 6.22


15 418199AA884555Hs.86603ESTs 3.55 6.22


440582AA993337Hs.129082ESTs 3.73 6.21


457766AL119470Hs.145631ESTs 3.69 6.21


426614AF036943Hs.172619KIAA1106 protein 4.71 6.21


412018BE148152 gb:RC4-HT0231-041199-012-b043.36 6.21
HT0231 Hamo


414699A1815523Hs.76930synuclein, alpha (non 3.68 6.19
A4 component of am


420127AA360399Hs.44811ESTs 3.54 6.18


418833AW974899Hs.292776ESTs 3.08 6.18


441265AA927180Hs.153261ESTs 3.21 6.17


413408851793Hs.21745ESTs 3.56 6.15


434512AW139932Hs.188941ESTs 3.56 6.15


422253W81526Hs.118329ESTs 5.04 6.10


439950AW937417Hs.293561ESTs 3.24 6.10


417210N99228Hs.49162ESTs 3.54 6.10


414306BE272198Hs.283869Human DNA sequence 3.35 6.10
from clone RPS-1013A2


411265AW834695 gb:RCO-LT0001-261199-031-D053.07 6.10
LT0001 Homo


412734AW993498 gb:RC2-BN0033-170300-019-b083.36 6.09
BN0033 Homo


425172AA447729Hs.12714ESTs 5.40 6.06


451759W23161Hs.32886ESTs 3.21 6.02


432154A1701523Hs.112577ESTs 3.50 6.02


35 401313c13p1435 exon 3.92 5.96


446951AI350575Hs.156730ESTs 3.20 5.95


440917AA909651Hs.160025ESTs 3.06 5.94


405961ph0_14521 exon 3.12 5.91


428737AA984728Hs.192760kinesin family member 3.05 5.90
5A


417292N69197Hs.191361ESTs 3.62 5.89


448681AL109781Hs.21754Homo Sapiens mRNA full3.52 5.88
length insert cDN


452524AW136499Hs.29796Homo Sapiens mRNA; 3.07 5.88
cDNA DKFZp434D1319
(f


426575M74826Hs.170808glutamate decarboxylase4.08 5.87
2 (pancreatic is


423641AL137256Hs.130489Homo Sapiens mRNA; 3.28 5.87
cDNA DKFZp761 K0912
(f


45 420755AI699437Hs.165268ESTs 3.17 5.86


448116AW352276Hs.170700ESTs 3.28 5.86


412694AW984373 gb:PM3-HN0011-200300-001-f013.00 5.83
HN0011 Homo


437612AA827715Hs.105153Homo sapiens cDNA FLJ142303.09 5.82
fis, clone NT


411522AW850286 gb:IL3-CT0219-161199-031-H113.26 5.81
CT0219 Homo


50 456910BE185921Hs.98073ESTs 3.20 5.80


d39915AI521791Hs.252358ESTs 3.55 5.80


404403c8p1 exon 3.23 5.80
1094


405332cNp3-13017 exon 3.51 5.78


411167AW820204 gb:OV2-ST0296-190100-029-c113.04 5.78
ST0296 Homo


55 416139H21109Hs.172853ESTs 3.63 5.77


434222AF119886Hs.283941Homo sapiens PR02591 3.65 5.77
mRNA, complete cds


415247F02431Hs.6581ESTs 3.08 5.75


446037A1076806Hs.282965ESTs 3.42 5.75


450478AW451709Hs.271200ESTs 3.80 5.72


60 446588AV659343Hs.282954ESTs 3.29 5.72


413118BE065939 gb:RC3-BT0319-100100-012-c113.03 5.72
BT0319 Homo


416946NM Hs.80545mitogen-activated protein3.91 5.72
012324 kinase 8 inter


454751AW819132 gb:RC3-ST0281-240400-015-c105T02813.06 5.72
Homo


457194H20669Hs.35406ESTs, Highly similar 3.54 5.71
to unnamed protein


65 438601AA811713Hs.163222ESTs 3.26 5.71


439032AA829487Hs.274412similarto yeast Upf3,variantA3.10 5.67


408940M585B3Hs.662cerebellin 1 precursor3.32 5.67


437700AA766060Hs.122848ESTs 3.23 5.66


416061845516Hs.26119ESTs 3.85 5.65


70 452861BE177663 gb:RC1-HT059&020300-011-h113.04 5.64
HT0598 Homo


430330AA476583Hs.132981ESTs 3.51 5.63


435312AJ243396Hs.4865voltage-gated sodium 5.67 5.62
channel beta-3 subu


400710c11p1_1297 exon 3.04 5.61


457130NM Hs.i83671lryptophan 2,3-dioxygenase3.31 5.60
005651


75 434513AF143888Hs.18213Homo Sapiens clone 3.93 5.60
IMAGE:121736 mRNA
seq


434277X77748Hs.3786glutamate receptor, 3.67 5.58
metabotropic 3


440854AW4d4900Hs.246715ESTs 3.30 5.58


457086AA412591Hs.2046B5ESTs 3.37 5.57


431883AA731404Hs.105510ESTs 3.67 5.56


400758AA158742Hs.225084Homo Sapiens cDNA FLJ142803.43 5.55
fis, clone PL


455374AW904039 gb:CM3-NN1040-200400-156-d033.36 5.52
NN1040 Hamo


440750AW105131Hs.245405ESTs 3.10 5.50


451865H43737Hs.33186ESTs, Weakly similar 3.38 5.50
to unknown protein


135


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453100AW806871Hs.224786ESTs 3.30 5.49


433940H05129Hs.7459cyclic AMP-regulated 3.24 5.49
phosphoprotein, 21


454935AW846075 gb:MR3-CT0176-081099-002-b023.26 5.48
CT0176 Homo


435447A1872932Hs.142442HP1-BP74 3 5
89 47


402953c20p3_3451 exon . .
3.28 5.47


456233AA203339 gb:zx56a01.r1 Soares 3.02 5.47
fetal_liver-spleen-


407718AW070784Hs.243243EST 3.30 5.45


417429A1950629Hs.286237Homo sapiens cDNA FLJ13.31 5.38
1 841 tis, clone HE


446408AI797169Hs.208486ESTs 3 5
07 37


1 441792AW873635Hs.143962ESTs . .
~ 3.19 5.35


-050661AW952160Hs.32916ESTs 3.70 5.35


433932AW954599Hs.169330neuronal protein 6.78 5.33


427002AA524093Hs.23158ESTs 4.00 5.32


428741AA461386 gb:zx70hO6.r1 Soares 3 5
total 10 32
fetus
Nb2HF8


1 446383T05816Hs.92511- . .
_ 3.39 5.30
_
EST


442988A1026130Hs.131683ESTs 3.07 5.29


426713A1655299Hs.130055ESTs 3.33 5.29


421294AA713486Hs.180291ESTs 3.44 5.28


406452ph2-21961 exon 3 5
20 28


423508AW604297Hs.129711hepatitis A virus cellular. .
receptor 1 3.26 5.27


442114BE217975Hs.157021ESTs 3.32 5.26


432508AI808915Hs.190201ESTs 3.46 5.26


425604094320Hs.158330neuropeptide Y receptorY53.26 5.23


417925826789Hs.23995ESTs 3 5
08 23


25 444448H66317Hs.143660ESTs . .
3.81 5.22


413024AF036268Hs.75149SH3-domain GR82-like 3.71 5.22
2


-037911AA848010Hs.124250ESTs . 3.11 5.18


435406F26698Hs.4884calciumlcalmodulin-dependent4.95 5.17
protein kin


407131898679 gb:yr31c03.s1Soaresfetalliverspleen3.30 5
16


435776AI537162Hs.263988ESTs 3.14 .
5.13


455532AW984828 gb:RC1-HN0015-120400-021-h113.14 5.13
HN0015 Homo


-057352AA489099 gb:aa56h09.s1 NCI-CGAP_GCB13.48 5.12
Homosapiens


428670AA43i682Hs.134832ESTs 3.17 5.12


445962A1268410Hs.201386ESTs 3 5
14 12


3 418153813696Hs.112830ESTs . .
5 3.16 5.10


440565AW103823Hs.131586ESTs 3.08 5.10


431446AW294929Hs.255369Homo Sapiens cDNA FLJ102653.42 5.09
fis, clone HE


456036BE536554Hs.75839zinc finger protein 3.21 5.09
6 (CMPXi )


420883AI735488Hs.111436ESTs 3 5
17 08


455528AW984757 gb:RC1-HN0015-040400-011-g10. .
HN0015 Homo 3.35 5.08


408442859608Hs.21435ESTs 3.10 5.07


446093A1346849Hs.145896ESTs 3.30 5.06


403489c3p1 exon 3.43 5.05
2255


405278cNp3_1070 exon 3 5
05 03


45 412804H18857Hs.22547ESTs . .
3.63 5.03


458407W90022Hs.186809ESTs, Highly similar 3.52 5.03
to LECT2 precursor


407367AA130773 gb:zo13dOt.r1 5tratagene3.51 5.02
colon (937204)


439108AW163034Hs.6467synaptogydn 3 5.63 5.01


445335A1220339Hs.166775ESTs 3 01
21 5


435404A1240661Hs.124995ESTs . .
3.99 5.00


TABLE 6B:
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
55 Accession: Genbank accession numbers
Pkey CAT Accession
Number


410837282574-1AW806917 AW866469 BF898475 BF898476 AW866540 AW866614
BE145698 AW866575


-036812659779AW978773 AW298067 AA810101 AW194180 AA731645 AI690673
1


4541711049240AW854832 AW854798 AW854857 AW854816 AW854834 AW854817
1


45458928039 BG674750 BF374578 AW810080 AW810106 AW810084 BF374755
6 AW809621 BF374734 BF374590 BF374594 AW809699 BF374588
AW810437


AW810161 AW809662 AW810151


4171592075888801760 N49787 801761
1


4593491027822AW749381 H93337
1


65 414187315279BE259777 BE312141 BF942980
1


423280881045AW955178 H86636 AA324037
1


4314001233916AW969094AA504607 AA504705
1


454566164604_1AW807605 AW807690 AW807677 AW807752 AW807673 AW807900
AW807955 AW807679 AW807615 AW807917 AW807849 AW807832
AW807821


AW807842 AW807827 AW807754 AW807830 AW807829 AW807825
7o AW807819 AW807769 AW807685 AW807603 AW807763 AW807612
AW807840


AW807908 AW807684 AW807609 AW807596 AW807595 AW807593
AW807907 AW807902 AW807846 AW807756 AW807687 AW807836
AW807835


AW807770 AW807753 AW807669 AW807678 AW807686 AW807680
AW807688 AW807847 AW807957 AW807674 AW807602 AW8076i7
AW807921


AW807667 AW807952 AW807918 AW807670 AW807760 AW807956
AW807608 AW807683 AW807839 AW807601 AW807822 AW807898


437948330397_1AA772920 D59870 D61151 AI591331 BF960996


4389191242618AW979114 AA828060 AA837606 AA829203
1


75 454578_ BE150647 AW971143 AW809224 AW809221 BF753820 AW809220
1670 AW809178 AW809150 AW809195 AW809175
3


4558361518824BE145800 BE145921 8E145873 BEi45871 BE145930 BE145797
1 BE145795


4549681085677_1AW848279 AW849039 AW847956 AW8d7957 AW8d9046 AW848698
AW849034 AW849033


4181622189291T11756 T20135 T19729 T11958T11816 845874
1


4311691235760AW971240 AA493723 AA493843
1


458172363900BE007237 BE546311 AA984819 81256810 W19919 BE007263
1 BG000322 BF327011 AA890198 BE007496


412172709034W04156 AW897535 N94221
1


427942465847BE543651 AA417856 AV756446 BG505084 81460307 81460993
1 BG613293


4546881066481BF375123 AW814472 AW814474 AW813343 AW816161 AW813380
1 AW813300


136


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455675 1490763_1 BE065984 BE066085 BE065942 BE065955
455644 1489561_1 BE064521 BE064441 BE064426 BE064285 BE064286
451496 85420 1 AA046879 BF327988 AW503407 AA018131
424617 895912-1 AW963059 AA344151 AA344472
454962 323094 1 AW853945 AW854083 BF962818 AW847791 81035483 AW847645 BF961514
BF963484 BF952264 BF963521
455260 231032 1 BE161805 AW8783i7 BE161759 BF8700328F869588
434589 14676 1 AF147363 T47219 T47218
410926 1064369 1 AW810708 AW810808 AW810771 AW810924
409623 830636 1 AW449665 BE220971 AW449185
1 ~ 437254 1239876 1 AW976161 AA831258 AA765857 AA747712 AI784019
415508 1874742_1 845579 F10822 839236
413263 1497122_1 BE075132 BE075131 BE075130 D60395 BF688035
415967 1899490 1 H49130 H11230 BF363165 H49061 H11124
417555 1978200 1 AA203678 AL597143 Hfi5366
1 S 413547 1520005 1 BE147456 BE147563 BE147708 BE147440
411132 1070974_1 AW819177 AW819242 AW819191 AW819175 AW819252 AW819244
AW819265 AW819269 AW819190 AW819268 AW819183 AW819246 AW819194
AW819249 AW819186 AW819180 AW819188 BE158470 AW819251 BE152602 AW819263
454568 1061859 1 AW807909 AW807824 AW807826 AW807903 AW807766 AW807750
AW807911 BE141434 AW807611 AW807837 AW807899 BF374481
413162 1492355 1 BE068104 BE068096 BE068198 BE0681i5 BE068102 BE068154
BE068103
455377 154707_1 BF947516 AW905291 BF947512 BF952606 BF952706 BF952525 BF952524
BF952619 BF947500 BF952fi08 BF952523 BF952532 BF952344
BF746516 BF947614 BF746511 BF952358 AW905400 AW905300 BF947617 AW905349
BF952531 AW905403 BF952528 BE081655 BF746513
AW905286 BF952868 BF947513 BF947510 BF947618 BF947619 AW905347
455149 1099453 1 AW861879 AW861948 AW858447 AW861873 AW858418 AW8fi1871
412686 1243154_1 AW984068 AW984077 AW984072
436383 46767-1 AJ227879 BE065178 BE065329
412290 1163352 1 BE069037 BE069178 AW936034 AW936025
411427 1083097 1 AW846080 AW846074 AW846118 AW846130
410816 1060611 1 AW806175 AW806176 AW806170 AW806156
447258 1485710 1 BE6i7316 BE047911 AA984167
3~ 455547 1245954 1 AW994078 BE176183
432209 1235790 1 AW971278 AA528270 AA553447 AW971281
411138 1071173 1 AW819500 AW819503 AW819481 AW819459 BF375618
454713 10678891 AW815111AW815094AW8152i8
455965 1555935 1 BE167014 BE167058 BE167062
3 5 416268 1959926 1 H41854 H49111 H46317
443100 416959 1 BE004743 AW804074 BE089437 BE089439 BE089378 BE089438 BE004795
W02375 A1033188 BF332422 BF332418 BE178660
408070 632273 1 AW148852 BG994152
425440 1228191 1 AW962960 AA357518 AA360531
412317 1164038 1 AW991979 AW991981 AW991983 AW936856 AW991977 AW991971
AW936852
453839 3209657 1 AL138417 AL138418
419392 215562_2 W28573 W27418
412018 147109 1 BE148133 BE148132 BF736564 BE148152 BE148159 BF893700
411265 1074383_1 AW834695 AW834717 AW834714
412734 1245451 1 AW993498 AW993484 AW993490 BF512974
45 412694 1243393 1 AW984388 AW984392 AW984379 AW984351 AW984381 AW984377
AW984366 AW98d3d8 AW984391 AW984373 AW984372 AW984353 AW984362
411522 1089092 1 BE143505 BF374i94 BF374190 AW850286
411167 1071740 1 AW820323 AW820314 AW820321
413118 1490760 1 BE066079 BE065939 BE065956
454751 1070838 1 AW819132 AW819122 AW819018 AW819135 AW819126 AW819024
AW819012 AW819141
452861 319757 1 BE177663 AW994738 AI923735 BF948431 BF948329
455374 1161013 1 AW904029 AW904030 AW904039 AW90d031 AW904032 AW90d046
454935 1083098 1 AW846075 AW846103 BF333976 AW846077 AW846122 AW846129
AW8d6095 AW846076 BF333979 BF333978 AW846092
456233 2635744 1 AA203339 AA906160 AA929005
428741 1384399 1 AA461386 AA433841 AA433845
55 455532 1243692_1 AW984828 AW984787 AW984806 AW984817 AW984826 AW98d822
AW984773 AW984786 AW984803 AW984796
457352 1233795 1 AW968968 AA489099 N72933AA489184
455528 1243660_1 AW984734 AW984757 AW984797 AW984745
407367 4907 1 AF085963 H72550 H72951 AA130773
C)O TABLE 60:
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank
Identifier (GI) numbers. "Dunham, et al." refers to the publication entitled
"The DNA
sequence of human chromosome 22" Dunham, et al. (1999) Nature 402:489-495.
Strand: Indicates DNA sUand from which exons were predicted.
N~position: Indicates nucleotide positions of predicted exons.
Pkey Ref Strand Nt_position
401412 7940103 Minus 43347-45776
405230 7249032 Minus 97493-97682

7~ 402125 4033680 Plus 172732-172868
404289 2769644 Plus 15049-15286,30267-30457
406534 7711477 Plus 40463-40586,41191-41336,41856-41986,4300
405348 2914717 Minus 43310-43462
401081 3478647 Plus 105163-105305
7J~ 402624 7885063 Minus 31308-31439
405320 3478667 Minus 118511-118926,119175-119331
405476 2121229 Plus 69890-70883
403932 7454203 Minus 8142-8753
406112 9133145 Plus 61863-62028
g o 400708 7249204 Plus 118115-119445
405427 7243901 Minus 6509-6729
402616 6723302 Minus 25104-25291
404541 8318559 Plus 103456-103664
137


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403008 6070396 Plus 94608-94785,95096.95233
403395 9438353 Minus 144947-145075
S 403061 8954192 Plus 142875.143008 ~,y'
403717 7259747 Minus 79166-79758 .~
401313 9212516 Minus 190842-191090
.


405961 8190197 Plus 45132 45254


404403 7272157 Minus 72053-72238


405332 3169141 Minus 70483-71207


400710 7249204 Plus 156753-157120
1 402953 9408724 Minus 122603-122743
O


406452 9588380 Minus 76322-76427


403489 7331314 Minus 38897 39212


405278 6139075 Minus 3863-3965,4823-4891,5439-5529.8043-6170


15 _


TABLE 7A: EXTENDED GUOBLASTOMA SEOUENCES~
This table includes sequence infarmafion
for 21 ONA and protein sequences
DNA sequence 1 (SEQ ID N0:367t


Gene name: Protein tyrosine phosphatase,
receptor-type, 2 polypeptide 1
0 Unigene number: Hs.78867
Probeset Accession #: M93426


Nucleic Acid Accession #: NM 002851


Coding sequence: 148-7092


1 11 21 31 41 51
2S CACACATACG CACGCACGAT CTCACTTCGA TCTATACACT60
GGAGGATTAA AACAAACAAA 120
CAAAAAAAAC ATTTCCTTCG CTCCCCCTCC CTCTCCACTC180
TGAGAAGCAG AGGAGCCGCA 240
O CGGCGAGGGG CCGCAGACCG TCTGGAA_ATG CGAATCCTAA300
AGCGTTTCCT CGCTTGCATT 360
CAGCTCCTCT GTGTTTGCCG CCTGGATTGG GCTAATGGAT420
? ACTACAGACA ACAGAGAAAA 480
CTTGTTGAAG AGATTGGCTG GTCCTATACA GGAGCACTGA540
ATCAAAAAAA TTGGGGAAAG 600
S AAATATCCAA CATGTAATAG CCCAAAACAA TCTCCTATCA660
ATATTGATGA AGATCTTACA 720
CAAGTAAATG TGAATCTTAA GAAACTTAAA TTTCAGGGTT780 - _
GGGATAAAAC ATCATTGGAA 840
O AACACATTCA TTCATAACAC TGGGAAAACA GTGGAAATTA900
ATCTCACTAA TGACTACCGT 960
GTCAGCGGAG GAGTTTCAGA AATGGTGTTT AAAGCAAGCA1020
AGATAACTTT TCACTGGGGA 1080
AAATGCAATA TGTCATCTGA TGGATCAGAG CATAGTTTAG1140
S AAGGACAAAA ATTTCCACTT 1200
GAGATGCAAA TCTACTGCTT TGATGCGGAC CGATTTTCAA1260
GTTTTGAGGA AGCAGTCAAA 1320
GGAAAAGGGA AGTTAAGAGC TTTATCCATT TTGTTTGAGG1380
TTGGGACAGA AGAAAATTTG 1440
O GATTTCAAAG CGATTATTGA TGGAGTCGAA AGTGTTAGTC1500
GTTTTGGGAA GCAGGCTGCT 1560
TTAGATCCAT TCATACTGTT GAACCTTCTG CCAAACTCAA1620
CfGACAAGTA TTACATTTAC 1680
AATGGCTCAT TGACATCTCC TCCCTGCACA GACACAGTTG1790
S ACTGGATTGT TTTTAAAGAT 1800
ACAGTTAGCA TCTCTGAAAG CCAG'FTGGCT GTTTTTTGTG1860
AAGTTCTTAC AATGCAACAA 1920
TCTGGTTATG TCATGCTGAT GGACTAC1'TA CAAAACAATT1980
TTCGAGAGCA ACAGTACAAG 2040
O TTCTCTAGAC AGGTGTTTTC CTCATACACT GGAAAGGAAG2100
AGATTCATGA AGCAGTTTGT 2160
AGTTCAGAAC CAGAAAATGT TCAGGCTGAC CCAGAGAATT2220
ATACCAGCCT TCTTGTTACA 2280
TGGGAAAGAC CTCGAGTCGT TTATGATACC ATGATTGAGA2340
S AGTTTGCAGT TTTGTACCAG 2400
CAGTTGGATG GAGAGGACCA AACCAAGCAT GAATTTTTGA2460
CAGATGGCTA TCAAGACTTG 2520
GGTGCTATTC TCAATAATTT GCTACCCAAT ATGAGTTATG2580
TTCTTCAGAT AGTAGCCATA 2640
O TGCACTAATG GCTTATATGG AAAATACAGC GACCAACTGA2700
TTGTCGACAT GCCTACTGAT 2760
AATCCTGAAC TTGATCTTTT CCGTGAATTA ATTGGAACTG2820
AAGAAATAAT CAAGGAGGAG 2880
7 GAAGAGGGAA AAGACATTGA AGAAGGCGCT ATTGTGAATC2940
CTGGTAGAGA CAGTGCTACA 3000
IS AACCAAATCA GGAAAAAGGA ACCCCAGATT TCTACCACAA3060
CACACTACAA TCGCATAGGG 3120
ACGAAATACA ATGAAGCCAA GACTAACCGA TCCCCAACAA3180
GAGGAAGTGA ATTCTCTGGA 3240
AAGGGTGATG TTCCCAATAC ATCTTTAAAT TCCACTTCCC3300
, AACCAGTCAC TAAATTAGCC 3360
ACAGAAAAAG ATATTTCCTT GACTTCTCAG ACTGTGACTG3420
AACTGCCACC TCACACTGTG 3480
GAAGGTACTT CAGCCTCTTT AAATGATGGC TCTAAAACTG3540
TTCTTAGATC TCCACATATG 3600
AACTTGTCGG GGACTGCAGA ATCCTTAAAT ACAGTTTCTA
TAACAGAATA TGAGGAGGAG
AGTTTATTGA CCAGTTTCAA GCTTGATACT GGAGCTGAAG
ATTCTTCAGG CTCCAGTCCC
GCAACTTCTG CTATCCCATT CATCTCTGAG AACATATCCC
AAGGGTATAT ATTTTCCTCC
GAAAACCCAG AGACAATAAC ATATGATGTC CTTATACCAG
AATCTGCTAG AAATGCTTCC
GAAGATTCAA CTTCATCAGG TTCAGAAGAA TCACTAAAGG
ATCCTTCTAT GGAGGGAAAT
GTGTGGTTTC CTAGCTCTAC AGACATAACA GCACAGCCCG
ATGTTGGATC AGGCAGAGAG
AGCTTTCTCC AGACTAATTA CACTGAGATA CGTGTTGATG
AATCTGAGAA GACAACCAAG
TCCTTTTCTG CAGGCCCAGT GATGTCACAG GGTCCCTCAG
TTACAGATCT GGAAATGCCA
CATTATTCTA CCTTTGCCTA CTTCCCAACT GAGGTAACAC
CTCATGCTTT TACCCCATCC
TCCAGACAAC AGGATTTGGT CTCCACGGTC AACGTGGTAT
ACTCGCAGAC AACCCAACCG
GTATACAATG GTGAGACACC TCTTCAACCT TCCTACAGTA
GTGAAGTCTT TCCTCTAGTC
ACCCCTTTGT TGCTTGACAA TCAGATCCTC AACACTACCC
CTGCTGCTTC AAGTAGTGAT
TCGGCCTTGC ATGCTACGCC TGTATTTCCC AGTGTCGATG
TGTCATTTGA ATCCATCCTG
TCTTCCTATG ATGGTGCACC TTTGCTTCCA TTTTCCTCTG
CTTCCTTCAG TAGTGAATTG
TTTCGCCATC TGCATACAGT TTCTCAAATC CTTCCACAAG
TTACTTCAGC TACCGAGAGT
GATAAGGTGC CCTTGCATGC TTCTCTGCCA GTGGCTGGGG
GTGATTTGCT ATTAGAGCCC
AGCCTTGCTC AGTATTCTGA TGTGCTGTCC ACTACTCATG
CTGCTTCAGA GACGCTGGAA
TTTGGTAGTG AATCTGGTGT TCTTTATAAA ACGCTTATGT
TTTCTCAAGT TGAACCACCC
AGCAGTGATG CCATGATGCA TGCACGTTCT TCAGGGCCTG
AACCTTCTTA TGCtTTGTCT
GATAATGAGG GCTCCCAACA CATCTTCACT GTTTCTTACA
GTTGTGCAAT ACCTGTGCAT
GATTCTGTGG GTGTAACTTA TCAGGGTTCC TTATTTAGCG
GCCCTAGCCA TATACCAATA
CCTAAGTCTT CGTTAATAAC CCCAACTGCA TCATTACTGC
AGCCTACTCA TGCCCTCTCT
GGTGATGGGG AATGGTCTGG AGCCTCTTCT GATAGTGAAT
TTCTTTTACC TGACACAGAT
GGGCTGACAG CCCTTAACAT TTCTTCACCT GTTTCTGTAG
CTGAATTTAC ATATACAACA
TCTGTGTTTG GTGATGATAA TAAGGCGCTT TCTAAAAGTG
AAATAATATA TGGAAATGAG
ACTGAACTGC AAATTCCTTC TTTCAATGAG ATGGTTTACC
CTTCTGAAAG CACAGTCATG
CCCAACATGT ATGATAATGT AAATAAGTTG AATGCGTCTT
TACAAGAAAC CTGTGTTTCC
ATTTCTAGCA CCAAGGGCAT GTTTCCAGGG TCCCTTGCTC
ATACCACCAC TAAGGTTTTT
GATCATGAGA TTAGTCAAGT TCCAGAAAAT AACTTTTCAG
TTCAACCTAC ACATACTGTC
TCTCAAGCAT CTr,GTGACAC TTCGCTTAAA CCTGTGCTTA
GTGCAAACTC AGAGCCAGCA



.;-: : ..~ ~' 1.','.
;<:;d CA 02459219 2004-03-17 . . . '
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t~"~ 'L.. ~it .'' ~ 1~'~:'h ~.;~'~t~ : ~'~'"~'' J'~a5)'i rrr~..i~-
~~


- ".~'~~.y='~.;~:
~:a':~ ~;..:


.. .
TCCTCTGACC CTGCTTCTAG TGAAATGTTA TCTCCTTCAA366V'
CTCAGCTCTT ATTTTATGAG


ACCTCAGCTT CTTTTAGTAC TGAAGTATTG CTACAACCTT3720
CCTTTCAGGC TTCTGATGTT


t
GACACCTTGC TTAAAACTGT TCTTCCAGCT GTGCCCAGTG3780
ATCCAATATT GGTTGAAACC


CCCAAAGTTG ATAAAATTAG TTCTACAATG TTGCATCTCA3840 ,
S TTGTATCAAA TTCTGCTTCA


AGTGAAAACA TGGTGCACTC TACATCTGTA CCAGTTTTTG3900
ATGTGTCGCC TACTTCTCAT


ATGCACTCTG CTTCACTTCA AGGTTTGACC ATTTCCTA,TG3960
CAAGTGAGAA ATATGAACCA


GTTTTGTTAA AAAGTGAAAG TTCCCACCAA GTGGTACCTT4020
CTTTGTACAG TAATGATGAG


TTGTTCCAAA CGGCCAATTT GGAGATTAAC CAGGCCCATC4080
CCCCAAAAGG AAGGCATGTA


TTTGCTACAC CTGTTTTATC AATTGATGAA CCATTAAATA4140
CACfAATAAA TAAGCTTATA


1 O CATTCCGATG AAATTTTAAC CTCC'ACCAAA AGTTCTGTTA4200
CTGGTAAGGT ATTTGCTGGT


ATTCCAACAG TTGCTTCTGA TACATTTGTA TCTACTGATC4260
ATTCTGTTCC TATAGGAAAT


"- GGGCATGTTG CCATTACAGC TGTTTCTCCC CACAGAGATG4320
GTTCTGTAAC GTCAACAAAG


TTGCTGTTTC CTTCTAAGGC AACTTCTGAG CTGAGTCATA4380
GTGCCAAATC TGATGCCGGT


TTAGTGGGTG GTGGTGAAGA TGGTGACACT GATGATGATG4440
1 S GTGATGATGA TGATGACAGA


GATAGTGATG GCTTATCCAT TCATAAGTGT ATGTCATGCT4500
CATCCTATAG AGAATCACAG


GAAAAGGTAA TGAATGATTC AGACACCCAC GAAAACAGTC4560
TTATGGATCA GAATAATCCA


ATCTCATACT CACTATLTGA GAATTCTGAA GAAGATAATA4620
GAGTCACAAG TGTATCCTCA


GACAGTCAAA CTGGTATGGA CAGAAGTCCT GGTAAATCAC4680
CATCAGCAAA 2GGGCTATCC


CAAAAGCACA ATGATGGAAA AGAGGAAAAT GACATTCAGA4740
CTGGTAGTGC TCTGCTTCCT


n CTCAGCCCTG AATCTAAAGC ATGGGCAGTT CTGACAAGTG4800
ATGAAGAAAG TGGATCAGGG


CAAGGTACCT CAGATAGCCT TAATGAGAAT GAGACTTCCA4860
CAGATTTCAG TTTTGCAGAC


ACfAATGAAA AAGATGCTGA TGGGATCCTG GCAGCAGGTG4920
ACTCAGAAAT AACTCCTGGA


TTCCCACAGT CCCCAACATC ATCTGTTACT AGCGAGAACT4980
CAGAAGTGTT CCACGTTTCA


r~ GAGGCAGAGG CCAGTAATAG TAGCCATGAG TCTCGTATTG5040
' " GTCTAGCTGA GGGGTTGGAA
S


G TCCGAGAAGA AGGCAGTTAT ACCCCTTGTG ATCGTGTCAG5100
CCCTGACTTT TATCTGTCTA


GTGGTTCTTG TGGGTATTCT CATCTACTGG AGGAAATGCT5160
TCCAGACTGC ACACTTTTAC


_ TTAGAGGACA GTACATCCCC TAGAGTTATA TCCACACCTC5220
CAACACCTAT CTTTCCAATT


TCAGATGATG TCGGAGCAAT TCCAATAAAG CACTTTCCAA5280
AGCATGTTGC AGATTTACAT


GCAAGTAGTG GGTTTACTGA AGAATTTGAG ACACTGAAAG5340
AGTTTTACCA GGAAGTGCAG


3O AGCTGTACTG TTGACTTAGG TATTACAGCA GACAGCTCCA5400
ACCACCCAGA CAACAAGCAC


AAGAATCGAT ACATAAATAT CGTTGCCTAT GATCATAGCA5460
GGGTTAAGCT AGCACAGCTT


GCi'GAAAAGG ATGGCAAACT GACTGATTAT ATCAATGCCA5520
ATTATGTTGA TGGCTACAAC


t AGACCAAAAG CTTATATTGC TGCCCAAGGC CCACTGAAAT5580
CCACAGCTGA AGATTTCTGG


l AGAATGATAT GGGAACATAA TGTGGAAGTT ATTGTCATGA5640
TAACAAACCT CGTGGAGAAA


3 S GGAAGGAGAA AATGTGATCA GTACTGGCCT GCCGATGGGA5700
GTGAGGAGTA CGGGAACTTT


CTGGTCACTC AGAAGAGTGT GCAAGTGCTT GCCTATTATA5760
CTGTGAGGAA TTTTACTCTA


AGAAACACAA AAATAAAAAA GGGCTCCCAG AAAGGAAGAC5820
CCAGTGGACG TGTGGTCACA


CAGTATCACT ACACGCAGTG GCCTGACATG GGAGTACCAG5880
AGTACTCCCT GCCAGTGCTG


ACCTTTGTGA GAAAGGCAGC CTATGCCAAG CGCCATGCAG5940
TGGGGCCTGT TGTCGTCCAC


4O TGCAGTGCTG GAGTTGGAAG AACAG,GCACA TATATTGTGC6000
TAGACAGTAT GTTGCAGCAG


ATTCAACACG AAGGAACTGT CAACATATTT GGCTTCTTAA6060
AACACATCCG TTCACAAAGA


AATTATTTGG TACAAACTGA GGAGCAATAT GTCTTCATTC6120
ATGATACACT GGTTGAGGCC


ATACTTAGTA AAGAAACTGA GGTGCTGGAC AGTCATATTC6180
ATGCCTATGT TAATGCACTC


CTCATTCCTG GACCAGCAGG CAAAACAAAG CTAGAGAAAC6240
AATTCCAGCT CCTGAGCCAG


A TCAAATATAC AGCAGAGTGA CTATTGTGCA GCCCTAAAGC6300
4S AATGCAACAG GGAAAAGAAT


CGAACTTCTT CTATCATCCC TGTGGAAAGA TCAAGGGTTG6360
GCATTTCATC CCTGAGTGGA


GAAGGCACAG ACTACATCAA TGCCTCCTAT ATCATGGGCT6420
ATTACCAGAG CAATGAATTC


ATCATTACCC AGCACCCTCT CCTTCATACC ATCAAGGATT6480
TCTGGAGGAT GATATGGGAC


CATAATGCCC AACTGGTGGT TATGATTCCT GATGGCCAAA6540
ACATGGCAGA AGATGAATTT


S O GTTTACrGGC CAAATAAAGA TGAGCCTATA AATTGTGAGA6600
GCTTTAAGGT rACTCTTATG


GCTGAAGAAC ACAAATGTCT ATCTAATGAG GAAAAAGTTA6660
TAATTCAGGA CTTTATCTTA


GAAGCTACAC AGGATGATTA TGTACTTGAA GTGAGGCACT6720
TTCAGTGTCC TAAATGGCCA


AATCCRGATA GCCCCATTAG TAAAACT2TT GAACTTATAA6780,
GTGTTATAAA AGAAGAAGCT


GCCAATAGGG ATGGGCCTAT GATTGTTCAT GATGAGCATG6840
GAGGAGTGAC GGCAGGAACT


S S TTCTGTGCTC TGACAACCCT TATGCACCAA CTAGAAAAAG6900
AAAATTCCGT GGATGTTTAC


CAGGTAGCCA AGATGATCAA TCTGATGAGG CCAGGAGTCT6960
TTGCTGACAT TGAGCAGTAT


CAGTTTCTCT ACAAAGTGAT CCTCAGCGTT GTGAGCACAA7020
GGCAGGAAGA GAATCCATCC


ACCTCTCTGG ACAGTAATGG TGCAGCATTG CCTGATGGAA7080
ATATAGCTGA GAGCTTAGAG


~r TCTTTAGTTT AACACAGAAA GGGGTGGGGG GACTCACATC~TGAGCATTGT7140
~ TT,TCCTCTT,C,
~


SO TTGATTTCCC AfiCACCTGAC 7200
CTAAAATTAG GCAGGAAAAT CAGTCTAGTT CTGTTATCTG


AGTAACTTTC ATGACATAGG ATTCTGCCGC CAAATTTATA?260
TCATTAACAA TGTGTGCCTT


TTTGCAAGAC TTGTAATTTA CTTATTATGT TTGAACTAAA7320
ATGATTGAAT TTTACAGTAT


TTCTAAGAAT GGAATTGTGG TATTTTTTTC TGTATTGATT7380
TTAACAGAAA ATTTCAATTT


ATAGAGGTTA GCiAATTCCAA ACTACAGAAA ATGTTTGTTT7440
TTAGTGTCAA ATTTTTAGCT


6S GTATTTGTAG CAATTATCAG GTTTGCTAGA AATATAACTT7500 ,
TTAATACAGT AGCCTGTAAA


TAAAACACTC TTCCATATGA TATTCAACAT TTTACAACTG7560
CAGTATTCAC GTAAAGTAGA


AATAATCTGT TACTTATTGT AAATACTGCC CTAGTGTCTC7620
CATGGACCAA ATTTATATTT


ATAATTGTAG ATTTTTATAT TTTACTACTG AGTCAAGTTT7680 ,
TCTAGTTCTG TGTAATTGTT


TAGTTTAATG ACGTAGTTCA TTAGCTGGTC TTACTCfACC7740'
AGTTTTCTGA CA11~TG'


. TGTTACCTAA GTCATTAACT TTGTTTCAGC ATGTAATTTTr.~~a4
~ AACTTfiTGTCi'~ft'A(z'A~ ~
/O


"
ATACCTTCAT TTTGAAAGAA GTTTTTATGA GAATAACACC
TTACCAAArsA T1'GT~.C~AT'~79~'0~


GGTTTTTATC CAAGGAATTG CAAAAATAAA TATAAATATT7920
GCCA~A14AA AAAAAAAHAA


AAAAAAAAHA ApAAAAlfAAp A


7S Protein seguence 1 (SEQ ID N0:368)


Gene name: Protein tyrosine phosphatase, tide 1
receptor-type, Z polypep


Tlnigene number: Ha.7886?


Protein Accession )#: NP_002842


Signal sequence: 1-20 '


g0 Pfam domain: Garb anhydrase L3B-300]


Transmembrane domains: 1639-1661


Cellular Localization: plasma membrane


1 11 21 31 41 51


,; ,'',., t~,..;;,. ~
A.


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~
a~
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CA 02459219 2004-03-17
MRILKRFLAC IQLLCVCRLD WANGYYRQQR KLVEEIGWSY60
TGALNQKNWG KKYPTCNSPK


QSPINIDEDL TQVNVNLKKL KFQGWDKTSL ENTFIHNTGK120
TVEINLTNDY RVSGGVSEMV


FKASKITFHW GKCNMSSDGS EHSLEGQKFP LEMQIYCFDA180
DRFSSFEEAV KGKGKLRALS


ILFEVGTEEN LDFKAIIDGV ESVSRFGKQA ALDpFILLNL240 !.
S LPNSTDKYYI YNGSLTSPPC


TDTVDWIVFK DTVSISESQL AVFCEVLTMQ QSGYVMLMDy300
LQNNFREQQY KFSRQVFSSY


TGKEEIHEAV CSSEPENVQA DPENYTSLLV TWERPRVVYb~ 360
TMIEKFAVLY QQLDGEDQTK


HEFLTDGYQD LGAILNNLLP NMSYVLQIVA ICTNGLYGKY420
SDQLIVDMPT DNPELDLFPE


LIGTEEIIKE EEEGKDIEEG AIVNPGRDSA TNQIRKKEPQ480
ISTTTHYNRI GTKYNEAKTN


RSPTRGSEFS GKGDVPNTSL NSTSQPVTKL ATEKDISLTSS40
I QTVTELPPHT VEGTSASLND
O


GSKTVLRSPH MNLSGTAESL NTVSITEYEE ESLLTSFKLD600
TGAEDSSGSS PATSAIPFIS


ENISQGYIFS SENPETITYD VLIPESARNA SEDSTSSGSE660
ESLKDPSMEG NVWFPSSTDI


TAQPDVGSGR ESFLQTNYTE IRVDESEKTT KSFSAGPVMS720
QGPSVTDLEM PHYSTFAYFP


TEVTPHAFTP SSRQQDLVST VNVVYSQTTQ PVYNGETPLQ780
PSYSSEVFPL VTPLLLDNQI


LNTTPAASSS DSALHATPVF PSVDVSFESI LSSYDGAPLL840
I PFSSASFSSS LFRHLHTVSQ
S


ILPQVTSATE SDKVPLHASL PVAGGDLLLE PSLAQYSDVL900
STTHAASETL EFGSESGVLY


KTLMFSQVEP PSSDAMldHAR SSGPEPSYAL SDNEGSQHIF960
TVSYSSAIPV HDSVGVTYQG


SLFSGPSHIP IPKSSLITPT ASLLQPTHAL SGDGEWSGAS1020
SDSEFLLPDT DGLTALNISS


PVSVAEFTYT TSVFGDDNKA LSKSEIIYGN ETELQIPSFN1080
EMVYPSESTV MPNMYDNVNK


.~ LNASLQETSV SISSTKGMFP GSLAHTTTKV FDHEISQVPE1140
GO NNFSVQPTHT VSQASGDTSL


KPVLSANSEP ASSDPASSEM LSPSTQLLFY ETSASFSTEV1200
LLQPSFQASD VDTLLKTVLP


AVPSDPILVE TPKVDKISST MLHLIVSNSA SSENMLHSTS1260
VPVFDVSPTS HMHSASLQGL


TISYASEKYE PVLLKSESSH QVVPSLYSND ELFQTANLEI1320
NQAHPPKGRH VFATPVLSID


EPLNTLINKL IHSDEILTST KSSVTGKVFA GIPTVASDTF1380
VSTDHSVPIG NGHVAITAVS


.~ PHRDGSVTST KLLFPSXATS ELSHSAKSDA GLVGGGEDGD1440 ''
GS TDDDGDDDDD RDSDGLSIHK


CMSCSSYRES QEKVMNDSDT HENSLMDQNN PISYSLSENS1500
EEDNRVTSVS SDSQTGMDRS


PGKSPSANGL SQKHNDGKSE NDIQTGSALL PLSPESKAWA1560
VLTSDEESGS GQGTSD9LNE


NETSTDFSFA DTNEKDADGI LAAGDSEITP GFPQSPTSSV1620
TSENSEVFHV SfiAEASNSSH


ESRIGLAEGL ESEKKAVIPL VIVSALTFIC LWLVGILIY 1680
WRKCFQTAHF YLEDSTSPRV


ISTPPTPIFP ISDDVGAIPI KHFPKHVADL HASSGFTEEF1740
3 ETLKBFYQfiV QSCTVDLGIT
O


ADSSNHPDNK HKNRYINIVA YDHSRVKLAQ LAEKDGKLTD1800
YINANYVDGY NRPKAYIAAQ


GPLKSTAEDF WRMIWEHNVE VIVMITNLVE KGRkKCDQYW1860
PADGSEEYGN FLVTQKSVQV


LAYYTVRNFT LRNTKIKKGS QKGRPSGRW TQYHYTQWPD 1920
MGVPEYSLPV LTFVRKAAYA


KRHAVGPVW HCSAGVGRTG TYIVLDSMLQ QIQHEGTVNI 1980
FGFLKHIRSQ RNYLVQTEEQ


YVFIHDTLVE AILSKETEVL DSHIHAYVNA LLIPGPAGKT2040
. KLEKQFQLLS QSNIQQSDYS
3
S


AALKQCNREK NRTSSIIPVE RSRVGISSLS GEGTDYINAS2100 '
YIMGYYQSNE FIITQHPLLH


TIKDFWRMIW DHNAQLVVMI PDGQNMAEDE FVYWPNKDEP2160
INCESFKVTL MAEEHKCLSN


EEKLIIQDFI LEATQDDYVL EVRHFQCPKW PNPDSPISKT2220
FELISVIKEE AANRI7GPMIV


_
HDEHGGVTAG TFCALTTLMH QLEKENSVDV YQVAKMINLM2280 -
RPGVFADIEQ YQFLYKVILS


4O LVSTRQEENP STSLDSNGAA LPDGNIAESL ESLV


DNA SEQUENCE 2 (SEQ ID N0:369)


Gene name: tyrosylprotein sulfotransferase
1


Unigene number: Hs.110903


Probeset Accession #: D61594
4S


Nucleic Acid Accession #: NM 003596


Coding sequence: 82-1194


1 11 21 31 41 51


GTAGACTGTC CATGGCCTGA ACATTTTCCG AAAATCATTT6
TGAGCAAAAT ATCTGTTTAA


0
S TAACAAGATA ACCACATCAA GATGGTTGGA AAGCTGAAGC120
O AGAACTTACT ATTGGCAT(':


CTGGTGATTA GTTCTGTGAC TGTGTTTTAC CTGGGCCAGC180
ATGCCATGGA ATGCCATCAC


CGGATAGAGG AACGTAGCCA GCCAGTCAAA TTGGAGAGCA240
CAAGGACCAC TGTGAGAACT


GGCCTGGACC TCAAAGCCAA CAAAACCfTT GCCTATCACA300
AAGATATGCC TTTAATATTT


ATTGGRGGTG TGCCTCGGAG TGGAACCACA CTCATGAGGG360
S CCATGCTGGA CGCACATCCT
S G
C


A 420
ATTCGCT GTGGAGAGGA AACCAGGGTC ATTCCCCGAA
TCCTGGCCCT GAAGCAGATG


TGGTCACGGT CAAGTAAAGA GAAGATCCGC CTGGATGAGG480
CTGGTGTTAC TGATGAAGTG


CTGGATTCTG CCATGCAAGC CTTCTTACTA GAAATTATCG540
TTAAGCATGG GGAGCCAGCC


CCTTATTTAT GTAATAAAGA TCCTTTTGCC CTGAAATCTT600
TAACTTACCT TTCTAGGTTA


TTCCCCAATG CCAAATTTCT CCTGATGGTC CGAGATGGCC660
60 GGGCATCAGT ACATTCAATG
ATTT


CTCGAA AAGTTACTAT AGCTGGATTT GATCTGAACA 720
GCTATAGGGA CTGTTTGACA


AAGTGGAATC GTGCTATAGA GACCATGTAT AACCAGTGTA780
TGGAGGTTGG TTATAAAAAG


TGCATGTTGG TTCACTATGA ACAACTTGTC TTACATCCTGB40
AACGGTGGAT GAGAACACTC


TTAAAGTTCC TCCAGATTCC ATGGAACCAC TCAGTATTGC900
ACCATGAAGA GATGATTGGG


AAAGCTGGGG GAGTGTCTCT GTCAAAAGTG GAGAGATCTA960
6S CAGACCAAGT AATCAAGCCA
GTCA


ATGTAG GAGCTCTATC AAAATGGGTT GGGAAGATAC 1020
CGCCAGATGT TTTACAAGAC


ATGGCAGTGA TTGCTCCTAT GCTTGCCAAG CTTGGATATG1080
ACCCATATGC CAACCCACCT


AACTACGGAA AACCTGATCC CAAAATTATT GAAAACACTC1140 '7~';~' ~
GAAGGGTCTA TAAGGGAGAA ,
'


TTCCAACTAC 1200
CTGACTTTCT TAAAGAAAAA CCACAGACTG AGCAAGTGGA
GTAGCAGAAC


.~ CAGGAGCCTC TTCCATACAT GAGGAAAGAT TGCTGCCTTT1260
O TCAGCAGAAG GGAAATTCCT


AGGATTGGCT GTCCCCTGCC AAGCTTGGTG GAGCGTCTGC1320
ACCTTGGCTG CGCCGCCTGT


GCATTTGCCA GTTTCCTCCC ACTGAGAGGA TGGAGGTGTC1380
CGCACAGCTT TGGGCCTCGT


GAGGGATCTG CCTCCTGAGC AAAGAGCTCT TGATCCCGAT1440
TTCATGCACA GCCCTGCAGT


AAGGAGCCCA GAAGGAACAT GTGTTTCCTG TTAAAACTCC1500
TCTTGTTCTC TTTTCTTACA


~7 TTATGACGTT TGTTTTCAAG GAGAGGGTTT AAAAATGGGA1560
S TCCTGTAAGC AGACTTGGGC
AGTCTCC
TT


T 1620
TGAAATAGGT TGTCTGTACA TGTTCTAATG TTTTGTAGAA
CACGTGTGCC


TGTTT TG TATTGATGTG AATAATATTA AATATCCTAA x680
TTATTTAATT CATTGTATTG
~


TTTCTC 1740
A GTTGGGAAAT TACCATTATA CATTTACAAC CTAATGACTT
TTGTATTTTA


'TTTTTCAAAA TAAAAGCTTT CAATGTGA


00 Protein sequence 2 (SEQ ID N0:370)


Gene name: tyrosylprotein sulfotransferase
1


Unigene number: Hs.110903


Protein Accession #: NP
003587


_
Signal sequence: 1-21


140


. ::,., , ' ' y
~ r a..~
CA 02459219 2004-03-17
' ~. i ~:dt I~;,d~ li'~~: .~'' ~' lidi: '~"~~~st";'iE~r '.~~~~.1~~ ,~i.,~x;;,
't~ ~h j r. s( . ;E, s ~w
_: , ~ ., ~ k r_. ~ ~f~~:~~~s~
'42 '~ .X.. ~.
Transmembrane domains: none found
Cellular Localization: plasma membrane
1 11 21 31 41 51
S MVGKLKQNLL LACLVIS$VT VFYLGQHAME CHHRIEERSQ PVKLESTRTT VRTGLDLKAN 60
KTFAYHKDMP LIFIGGVPRS GTTLMRAMLD AHPDIRCGEE TRVIPRILAL KQMWSRSSKE 120
KIRLDEAGVT DEVLDSAMQA FLLEIIVKHG EPAPYLCNKD PFALKSLTYL SRLFPNAKFL 180
LMVRDGRASV HSMISRKVTI AGFDLNSYRD CLTKWNRAIE TMYNQCMEVG YKKCMLVHYE 240
QLVLHPERWM RTLLKFLQIP WNHSVLHHEE MIGKAGGVSL SKVERSTDQV IKPVNVGALS 300
1 Q KWVGKIPPDV LQDMAVIAPM LAKLGY17PYA NPPNYGKPDP KIIENTRRVY KGEFQLPDFL 360
KEKPQTEQVE
DNA sequence 3 (SEQ ID N0:371)


Gene name: interleukxn 13 receptor, alpha ,
1 S 2


Unigene number: Hs.25954


Probeset Accession #: 852795


Nucleic Acid ACCession #: NNI_000640 ; ' s
C
di
94
23


o
ng sequence:
-1
6


1 11 21 31 41 51


CGGATGAAGG CTATTTGAAG TCGCCATAAC CTGGTCAGAA60
GTGTGCCTGT CGGCGGGGAG


AGAGGCAATA TCAAGGTTTT AAATCTCGGA GAAATGGCTT120
TCGTTTGGTT GGCTATCGGA


TGCTTATATA CCTTTCTGAT AAGCACAACA TTTGGCTGTA180 ,
CTTCATCTTC AGACACCGAG


ATAAAAGTTA ACCCTCCTCA GGATTTTGAG ATAGTGGATC240
ZS CCGGATACTT AGGTTATCTC


TATTTGCAAT GGCAACCCCC ACTGTCTCTG GATCATTTTA300
AGGAATGCAC AGTGGAATAT


GAACTAAAAT ACCGAAACAT TGGTAGTGAA AG1TGGAAGA360
CCATCATTAC TAAGAATCTA


CATTACAAAG ATGGGTTTGA TCTTAACAAG GGCATTGAAG420
CGAAGATACA CACGCTTTTA


CCATGGCAAT GCACAAATGG ATCAGAAGTT CAAAGTTCCT480
GGGCAGAAAC TACTTATTGG


ATATCACCAC AAGGAATTCC AGAAACTAAA GTTCAGGATA540
3O TGGATTGCGT ATATTACAAT


TGGCAATATT TACTCTGTTC TTGGAAACCT GGCATAGGTG600
TACTTGTTGA TACCAATTAC


AACTTGTTTT ACfGGTATGA GGGCTTGGAT CATGCATTAC660
AGTGTGTTGA TTACATCAAG


GCTGATGGAC AAAATATAGG ATGCAGATTT CCCTATTTGG720 '
AGGCATCAGA CTATAAAGAT


TTCTATATTT GTGTTAATGG ATCATCAGAG AACAAGCCTA780
TCAGATCCAG TTATTTCACT


TTTCAGCTTC AAAATATAGT TAAACCTTTG CCGCCAGTCT840
3 S ATCTTACTTT TACTCGGGAG


AGTTCATGTG AAATTAAGCT GAAATGGAGC ATACCTTTGG900
GACCTATTCC AGCAAGGTGT


TTTGATTATG AAATTGAGAT CAGAGAAGAT GATACTACCT960
TGGTGACTGC TACAGTTGAA


AATGAAACAT ACACCTTGAA AACAACAAAT GAAACCCGAC1020
AATTATGCfT TGTAGTAAGA


AGCAAAGTGA ATATTTATTG CTCAGATGAC GGAATTTGGA1080 -
GTGAGTGGAG TGATAAACAA


TGCTGGGAAG GTGAAGACCT ATCGAAGAAA ACTTTGCTAC1140
~I GTTTCTGGCT ACCATTTGGT
O


TTCATCTTAA TATTAGTTAT ATxTGT)1ACC GGTCTGCTTT1200
TGCGTAAGCC AAACACCTAC


CCAAAAATGA TTCCAGAATT TTTCTGTGAT ACATGAAGAC1260
TTTCCATATC AAGAGACATG


GTATTGACTC AACAGTTTCC AGTCATGGCC AAATGTTCAA1320
TATGAGTCTC AATAAACTGA


ATTTTTCTTG CGAAAAAAAA AAAAAAAAAA AAAAAAAAAA1380
AAAAAAAAAA AAAAA?1AAAA


4S


Protein seguence 3 (SEQ ID N0:372)


Gene name: xnterleukin 13 receptor, alpha
2


Unxgene number: Hs.25954


n Probeset Accession #: 852795 .
S


V Protein Accession # NP_000631


Signal sequence: 1-23


FN3 domain: 155-322


Tranemembrane domains: 340-362


Cellular Localization: plasma membrane
SS 1


11 21 31 41 51


MAFVCLAIGC LYTFLISTTF GCTSSSDTEI KVNPPQDFEI60
VDPGYLGYLY LQWQPPLSLD


HFKECTVEYE LKYRNIGSET WKTIITKNLH YKDGFDLNKG120
IEAKIHTLLP WQCTNGSEVQ


SSWAETTYWI SPGIPETKV QDMDCVYYNW QYLLCSWKPG 180
IGVLLDTNYN LFYWYEGLDH


ALQCVDYIKA DGQNIGCRFP YLEASDYKDF YICVNGSSEN240
KpIRSSYPTF QLQNIVKPLP


PVYLTFTRES SCEIKLKWSI PLGPIPARCF DYEIEIRE'DD300
TTLVTATVEN ETYTLKTTNE


TRQLCFWRS XVNIYCSDDG IWSEWSDKQC WEGEDLSKKT 360
LLRFWLPFGF ILILVIFVTG


LLLRKPNTYP KMIPEFFCDT


6S DNA sequence 4 (SEQ ID N0:373)


Gene name: chemokine (C-X3-C) receptor 1


Unigene number: Hs.78913


Probeset Accession #: U20350


~~ Nucleicyd Accession #: NNI_001337
7~ '~~
'


~
Codmg
~
ence: 46-1113 .


,
' 1 11 21 31 41 S1


~ CAGATC CAGATTCCCT TTGCAGTCCA CGCCAGGCCT 60
TCACC
ATGGA TCAGTTCCCT
C~


_ 120
,CAGTGA CAGAAAACTT TGAGTACGAT GATTTGGCfG
AGGCCTGTTA TATTGGGGAC


7S ATCGTGGTCT TTGGGACTGT GTTCCTGTCC ATATTCTACT180
CCGTCATCTT TGCCATTGGC


CTGGTGGGAA ATTTGTTGGT AGTGTTTGCC CTCACCAACA240
GCAAGAAGCC CAAGAGTGTC


ACCGACATTT ACCTCCTGAA CCTGGCCTTG TCTGATCTGC300
TGTTTGTAGC CACTTTGCCC


TTCTGGACTC ACTATTTGAT AAATGAAAAG GGCCTCCACA360
ATGCCATGTG CAAATTCACT


p ACCGCCTTCT TCTTCATCGG CTTTTTTGGA AGCATATTCT420
~ O TCATCACCGT CATCAGCATT


.,~j~sGATAGGTACC TGGCCATCGT CCTGGCCGCC AACTCCATGA480
ACAACCGGAC CGTGCAGCAT


GGCGTCACCA TCAGCCTAGG CGTCTGGGCA GCAGCCATTT540
TGGTGGCAGC ACCCCAGTTC


ATGTTCACAA AGCAGAAAGA AAATGAATGC CTTGGTGACT600
ACCCCGAGGT CCTTCAGGAA


ATCTGGCCCG TGCTCCGCAA TGTGGAAACA AATTTTCTTG660
GCTTCCTACTCCCCCTGCTC


ATTATGAGTT ATTGCTACTT CAGAATCATC CAGACGCTGT720
TTTCCTGCAA GAACCACAAG


141
.~ .~~...


CA 02459219 2004-03-17
x .. ...~.. , I ~ ~.. ,~ 1(~ . ~~ v ~" I. 1 1
r .: ~ ~ M.,(I ~n(~ (]"n, e' h 1 '~i
, i)~. .~~~~'
.~IS !SIt


~.k_,~"f~-:'I,.


W ' ~'1~~'


AAAGCCAAAG CCATTAAACT GATCCTTCTG GTGGTCATCG780
TGTTTTTCCT CTTCTGGACA


CCCTACAACG TTATGATTTT CCTGGAGACG CTTAAGCTCT840
ATGACTTCTT TCCCAGTTGT


GACATGAGGA AGGATCTGAG GCTGGCCCTC AGTGTGACTG900
AGACGGTTGC ATTTAGCCAT


TGTTGCCTGA ATCCTCTCAT CTATGCATTT GCTGGGGAGA960
S AGTTCAGAAG ATACCTTTAC


CACCTGTATG GGAAATGCCT GGCTGTCCTG TGTGGGCGCT1020
CAGTCCACGT TGATTTCTCC


TCATCTGAAT CACAAAGGAG CAGGCATGGA AGTGTTGTGA1080
GCAGCAATTT TACTTACCAC


ACGAGTGATG GAGATGCATT GCTCCTTCTC TGAAGGGAAT1140
CCCAAAGCCT TGTGTGTACA


GAGAACCTGG AGTTCCTGAA CCTGATGCTG ACTAGTGAGG1200
AAGATTTTTG TTGTTATTTC


TTACAGGCAC AAAATGATGG ACCCAATGCA CACAAAACAA1260
I CCCTAGAGTG TTGTTGAGAA
O


TTGTGCTCAA AATTTGAAGA ATGAACAAAT TGAACTCTTT1320
GAATGACAAA GAGTAGACAT


TTCTCTTACT GCAAATGTCA TCAGAACTTT TTGGTTTGCA1380 _
GATGACAAAA ATTCAACTCA


GACTAGTTTA GTTAAATGAG GGTGGTGAAT ATTGTTCATA1440
TTGTGGCACA AGCAAAAAGG


GTGTCTGAGC CCTCAAAGTG AGGGGAACCA GGGCCTGAGC,
CAAGCTA


1 Protein sequence 4 (SEQ ID N0:374)
S


Gene name: chemokxne (C-X3-C) receptor
1


Unigene number: Hs.78913


Protein Accession #: NP_001328


Signal sequence: 1-44 '
20


pfam domain: 7tm 1 [48-2931


Cellular Localization: plasma membrane


1 11 21 31 41 51


MDQFPESVTE NFEYDDLAEA CYIGDIWFG TVFLSIFYSV60
ZS IFAIGLVGNL LWFALTNSK


KPKSVTDIYL LNLALSDLLF VATLPFWTHY LINEKGLHNA120
MCKFTTAFFF IGPFGSIFFI


TVISIDRYLA IVLAANSMNN RTVQHGVTIS LGVWAAAILV180
AAPQFMFTKQ KENECLGDYP


EVLQEIWPVL RNVETNFLGF LLPLLIMSYC YFRIIQTLFS240
CKNHKKAKAI KLILLWIVF


FLFWTPYNVM IFLETLKLYD FFPSCDMRKD LRLALSVTET300
VAFSHCCLNP LIYAFAGEKF


RRYLYHLYGK CLAVLCGRSV HVDFSSSESQ RSRHGSVLSS
NFTYHTSDGD ALLLL


DNA sequence 5 (SEQ ID N0:375) ,


Gene name: cannabinoid receptor 1 (brain)


Unigene number: Hs.75110 '


Probeset Accession #: 412986
3
S


Nucleic Acid Accession #: NM_001840


Coding sequence: 92-1510


1 11 21 31 41 51 _


,~ TCGGCTTATT TGTTTTCCCT CCTGTTAGGA TTGCCCCCTG60
' TGGGTCAGTT TCTCAGTCAT
O


t TTTGAGCTCA GCCTAATCAA AGAC~T~AGGT TA_TGAAGTCG120
ATCCTAGATG GCCTTGCAGA


TACCACCTTC CGCACCATCA CCACTGACCT CCTGTACGTG180
GGCTCAAATG ACATTCAGTA


CGAAGACATC AAAGGTGACA TGGCATCCAA ATTAGGGTAC240
TTCCCACAGA AATTCCCTTT


AACTTCCTTT AGGGGAAGTC CCTTCCAAGA GAAGATGAGT300
GCGGGAGACA ACCCCCAGCT


~ AGTCCCAGCA GACCAGGTGA ACATTACAGA ATTTTACAAC360
S AAGTCTCTCT CGTCCTTCAA


't GGAGAATGAG GAGAACATCC AGTGTGGGGA GAACTTCATG420
GACATAGAGT GTTTCATGGT


CCTGAACCCC AGCCAGCAGC TGGCCATTGC AGTCCTGTCC480
CTCACGCTGG GCACCTTCAC


GGTCCTGGAG AACCTCCTGG TGCTGTGCGT CATCCTCCAC540
TCCCGCAGCCTCCGCTGCAG


GCCTTCCTAC CACTTCATCG GCAGCCTGGC GGTGGCAGAC.CTCCTGGGGA600
GTGTCATTTT


TGTCTACAGC TTCATTGACT TCCACGTGTT CCACCGCAAA660
SO GATAGCCGCA ACGTGTTTCT


GTTCAAACTG GGTGGGGTCA CGGCCTCCTT CACTGCCTCC720
GTGGGCAGCC TGTTCCTCAC


AGCCATCGAC AGGTACATAT CCATTCACAG GCCCCTGGCC780
TATAAGAGGA TTGTCACCAG


GCCCAAGGCC GTGGTGGCGT TTTGCCTGAT GTGGACCATA840
GCCATTGTGA TCGCCGTGCT


GCCTCTCCTG GGCTGGAACT GCGAGAAACT GCAATCTGTT900
TGCTCAGACA TTTTCCCACA


CATTGATGAA ACCTACCTGA TGTTCTGGAT CGGGGTCACC960
S AGCGTACTGC TTCTGTTCAT
S


CGTGTATGCG TACATGTATA TTCTCTGGAA GGCTCACAGC1020
CACGCCGTCC GCATGATTCA


GCGTGGCACC CAGAAGAGCA TCATCATCCA CACGTCTGAG1080
GATGGGAAGG TACAGGTGAC


CCGGCCAGAC CAAGCCCGCA TGGACATTAG GTTAGCCAAG1140
ACCCTGGTCC TGATCCTGGT


GGTGTTGATC ATCTGCTGGG GCCCTCTGCT TGCAATCATG1200
GTGTATGATG TCTTTGGGAA


GATGAACAAG CTCATTAAGA CGGTGTTTGC ATTCTGCAGT1260
60 ATGCTCTGCC TGCTGAACTC


CACCGTGAAC CCCATCATCT ATGCPCTGAG GAGTAAGGAC1320
CTGCGACACG CTTTCCGGAG


CATGTTTCCC TCTTGTGAAG GCACfGCGCA GCCTCTGGAT1360
AACAGCATGG GGGACTCGGA


CTGCCTGCAC AAACACGCAA ACAATGCAGC CAGTGTTCAC1440 .
AGGGCCGCAG AAAGCTGCAT


CAAGAGCACA GTCAAGATTG CCAAGGTAAC CATGTCTGTG1500
TCCACAGACA CGTCTGCCGA


GGCTCTG_TGA GCCTGATGGC TCCCTGGCAG CACAGGAAAA1560
6S GAATTTTTTT TTTTAAGCTC
~


AAAATCTAGA AGAGTCTATT GTCTCCTTGG TTATATTTTT1620
TTAACTTTAC CATGCTCAAT


GAAAAGGTGA TTGTCACCAT GATCACTTAT CAGTTTGCTA1680
ATGTTTCCAT AGTTTAGGTA


CTCAAACTCC ATTCTCCAGG GGTTTACAGT GAAGAAAGCC1740
TGTTGTTTAA GTGACTGAAC


GATCCTTCAA AGTCTCAATG AAATAGGAGG GAAACCTTTG1800
GCTACACAAT TGGAAGTCTA


AGAACCCATG GAAAAATGCC ATCAAATGAA TAATGCCTTT1860
7O GTAACCACAA CTTTCACTAT


AATGTGAAAT GTAACTGTCC GTAGTATCAG AGATGTCCAT1920
TTTTACAAGT TATAGTACTA


GAGATATTTT GTAAAATGTA TTATGTCCTG TGAGATGTGT1980
ATCAGTGTTT ATGTGCTATT


AATATTTGTT TAGTTCAGCC AAACTGAAAG GTAGACTTTT2040
ATGAGAACAA TGGACAAGCA


GTGGATACGT GTCAATGTGT GCACTTTTTT TCTATATTAT2100
TGCCCATGAT ATAACTTTAG


~S AAATAAACCT TAATATTTCT TCCCAAAAAA AAAAA
'


Protein sequence 5 (SEQ i0 N0:376)


Gene name: cannabinoid receptor 1 (brain)


Unigene number: Hs.75110


Protein Accession #: NP 001831
$O


Signal sequence: none found


Pfam domain: 7tm 1 [133-397]


Transmembrane domains: 121-143, 156-178, 8, 344-366,
195-217, 237-259, 276-29 378-400


Cellular Localization: plasma membrane


1 11 21 31 41 51


. . . 142
.r, ..1.r .





CA 02459219 2004-03-17 t,v.
,. .
..
I


MKSILDGLAD TTFRTITTDL LYVGSNDIQY EDZKGDMASK 60
LGYFPQKFPL TSFRGSPFQB


KMTAGDNPQL VPADQVNITE FYNKSLSSFK ENEENIQCGE 120
NFMDIECPMV LNPSQQLAIA


VLSLTLGTFT VLENLLVLCV ILHSRSLRCR PSYHFIGSLA 180
VADLLGSVIF VYSFIDFHVF
S
SF
KLGGVT
S


HRKDSRNVFL F 24Qt '
A y ~~
TASVG
LFLT AIDRYISIHR PLAYKRIVTR PKAWAFCLM


WTIAIVIAVL PLLGWNCEKL QSVCSDIFPH IDETYLMFWI a
GVTSVLLLFI VYAYMYILWK 300'


AHSHAVRMIQ RGTQKSIIIH TSEDGKVQVT RPDQARMDIR 360
LAKTLVLILV VLIICWGPLL


AIMVYDVFGK MNKLIKTVFA FCSMLCLLNS TVNPIIYALR 420
SKDLRHAFRS MFPSCEGTAQ


O PLDNSMGDSD CLHKHANNAA SVHRAAESCI KSTVKIAKVT
MSVSTDTSAE AL


DNA sequence 6 (SEQ ID N0:377)


Gene name: endothelia receptor type B


Unigene number: He.82002


Probeset Accession #: D13168


1 Nucleic Acid Accession #: NM_000115
1
S


Coding sequence: 238-1566


1 11 21 31 41 51


GAGACATTCC GGTGGGGGAC TCTGGCCAGC CCGAGCAACG60
TGGATCCTGA GAGCACTCCC


ZO AGGTAGGCAT TTGCCCCGGT GGGACGCCTT GCCAGAGCAG120
TGTGTGGCAG GCCCCCGTGG


AGGATCAACA CAGTGGCTGA ACACTGGGAA GGAACTGGTA180
CTTGGAGTCT GGACATCTGA


AACTTGGCTC TGAAACTGCG CAGCGGCCAC CGGACGCCTT240
CTGGAGCAGG TAGCAGC_ATG


CAGCCGCCTC CAAGTCTGTG CGGACGCGCC CTGGTTGCGC300
TGGTTCTTGC CTGCGGCCTG


TCGCGGATCT GGGGAGAGGA GAGAGGCTTC CCGCCTGACA360
GGGCCACTCC GCTTTTGCAA


2S ACCGCAGAGA TAATGACGCC ACCCACTAAG ACCTTATGGC420
CCAAGGGTTC CAACGCCAGT


GTGGCGCGGT CGTTGGCACC TGCGGAGGTG CCTAAAGGAG480
ACAGGACGGC AGGATCTCCG


CCACGCACCA TCTCCCCTCC CCCGTGCCAA GGACCCATCG540
AGATCAAGGA GACTTTCAAA


TACATCAACA CGGTTGTGTC CTGCGTTGTG TTCGTGCTGG600
GGATCATCGG GAACTCCACA


2 CTTCTGAGAA TTATCTACAA GAACAAGTGC ATGCGAAACG660
O GTCCCAATAT CTTGATCGCC


.J AGCTTGGCTC TGGGAGACCT GCTGCACATC GTCATTGACA720
TCCCTATCAA TGTCTACAAG


CTGCTGGCAG AGGACTGGCC ATTTGGAGCT GAGF~TGTGTA780
AGCTGGTGCC TTTCATACAG


AAAGCCTCCG TGGGAATCAC TGTGCTGAGT CTATGTGCTC890
TGAGTATTGA CAGATATCGA


GCTGTTGCTT CTTGGAGTAG AATTAAAGGA ATTGGGGTTC900
CAAAATGGAC AGCAGTAGAA


ATTGTTTTGA TTTGGGTGGT CTCTGTGGTT CTGGCTGTCC960
3 CTGAAGCCAT AGGTTTTGAT
S


ATAATTACGA TGGACTACAA AGGAAGTTAT CTGCGAATCT1020
GCTTGCTTCA TCCCGTTCAG


AAGACAGCTT TCATGCAGTT TTACAAGACA GCAAAAGATT1080
GGTGGCTGTT CAGTTTCTAT


TTCTGCTTGC CATTGGCCAT CACTGCATTT TTTTATACAC1140
TAATGACCTG TGAAATGTTG


_
AGAAAGAAAA GTGGCATGCA GATTGCTTTA AATGATCACC1200
TAAAGCAGAG ACGGGAAGTG


~ GCCAAAACCG TCTTTTGCCT GGTCCTTGTC TTTGCCCTCT1260
40 GCTGGCTTCC CCTTCACCTC


AGCAGGATTC TGAAGCTCAC TCTTTA,TAAT CAGAATGATC1320
CCAATAGATG TGAACTTTTG


AGCTTTCTGT TGGTATTGGA CTATATTGGT ATCAACATGG1380
CTTCACTGAA TTCC2GCATT


AACCCAATTG CTCTGTATTT GGTGAGCAAA AGATTCAAAA1440
ACTGCTTTAA GTCATGCTTA


TGCTGCTGGT GCCAGTCATT TGAAGAAAAA CAGTCCTTGG1500
AGGAAAAGCA GTCGTGCTTA


AAGTTCAAAG CTAATGATCA CGGATATGAC AACTTCCGTT1560
CCAGTAATAA ATACAGCTCA


~ TCT_TGAAAGA AGAACTATTC ACTGTATTTC ATTTTCTTTA1620
't5TATTGGACCG AAGTCATTAA


AACAAAATGA AACATTTGCC AAAACAAAAC AAAAAACTAT1680
GTATTTGCAC AGCACACTAT


TAAAATATTA AGTGTAATTA TTTTAACACT CACAGCTACA1740
TATGACATTT TATGAGCTGT


TTACGGCATG GAAAGAAAAT CAGTGGGAAT TAAGAAAGCC1800
TCGTCGTGAA AGCACTTAAT


TTTTTACAGT TAGCACTTCA ACATAGCTCT TAACAACTTC1860
SO CAGGATATTC ACACAACACT


TAGGCTTAAA AATGAGCTCA CTCAGAATTT CTATTCTTTC1920
TAAAAAGAGA TTTATTTTTA


.AATCAATGGG ACTCTGATAT AAAGGAAGAA TAAGTCACTG1980
TAAAACAGAA CTTTTAAATG


AAGCTTAAAT TACTCAATTT AAAATTTTAA AATCCTTTAA2040
AACAACTTTT CAATTAATAT


TATCACACTA TTATCAGATT GTAATTAGAT GCAAATGAGA2100
GAGCAGTTTA GTTGTTGCAT


TTTTCGGACA CTGGAAACAT TTAAATGATC AGGAGGGAGT2160
AACAGAAAGA GCAAGGCTGT


SS TTTTGAAAAT CATTACACTT TCACTAGAAG CCCAAACCTC2220
AGCATTCTGC AATATGTAAC


CAACATGTCA CAAACAAGCA GCATGTAACA GACTGGCACA2280
TGTGCCAGCT GAATTTAAAA


TATAATACTT TTAAAAAGAA AATTATTACA TCCTTTACAT2340
TCAGTTAAGA TCAAACCTCA


CAAAGAGAAA TAGAATGTTT GAAAGGCTAT CCCAAAAGAC2400
TTTTTTGAAT CTGTCATTCA


CATACCCTGT GAAGACAATA CTATCTACAA TTTTTTCAGG2460
ATTATTAAAA TCTTCTTTTT


TCACTATCGT AGCTTAAACT GTGTTTGGTT TTGTCATCTG2520
TAAATACTTA CCTACATACA


CTGCATGTAG ATGATTAAAT GAGGGCAGGC CCTGTGCTCA2580
TAGCTTTACG ATGGAGAGAT


GCCAGTGACC TCATAATAAA GACTGTGAAC TGCCTGGTGC2640
AGTGTCCACA TGACAAAGGG


GCAGGTAGCA CCCTCTCTCA CCCATGCTGT GGTTAAAATG2700
GTTTCTAGCA TATGTATAAT


GCTATAGTTA AAATACTATT TTTCAAAATC ATACAGATTA2760
GTACATTTAA CAGCTACCTG


6S TAAAGCTTAT TACTAATTTT TGTATTATTT TTGTAAATAG2820 ,
CCAATAGAAA AGTTTGCTTG


ACATGGTGCT TTTCTTTCAT CTAGAGGCAA AACTGCTTTT2880
TGAGACCGTA AGAACCTCTT


AGCTTTGTGC GTTCCTGCCT AATTTTTATA TCTTCTAAGC2940
AAAGTGCCTT AGGATAGCTT


GGGATGAGAT GTGTGTGAAA GTATGTACAA GAGAAAACGG3000
AAGAGAGAGG AAATGAGGTG


GGGTTGGAGG AAACCCATGG GGACAGATTC CCATTCTTAG3060
CCTAACGTTC GTCATTGCCT


7O CGTCACATCA ATGCAAAAGG TCCTGATTTT GTTCCAGCAA3120
AACACAGTGC AATGTTCTCA


GAGTGACTTT CGAAATAAAT TGGGCCCAAG AGCTTTAACT3180
CGGTCTTAAA ATATGCCCAA


ATTTTTACTT TGTTTTTCTT TTAATAGGCT GGGCCACATG3240
TTGGAAATAA GCTAGTAATG


TTGTTTTCTG TCAATATTGA ATGTGATGGT ACAGTAAACC3300
AAAACCCAAC AATGTGGCCA


GAAAGAAAGA GCAATAATAA TTAATTCACA CACCATATGG3360
ATTCfATTTA TAAATCACCC


~7 ACAAACTTGT TGTTTAATTT CATCCCAATC ACTTTTTCAG3420
/S AGGCCTGTTA TCATAGAAGT


CATTTTAGAC TCTCAATTTT AAATTAATT2 TGAATCACTA3480
ATATTTTCAC AGTTTATTAA


TATATTTAAT TTCTATTTAA ATTTTAGATT ATTTTTATTA3540
CCATGTACTG AATTTTTACA


TCCTGATACC CTTTCCTTCT CCATGTCAGT ATCATGTTCT3600
CTAATTATCT TGCCAAATTT


TGAAACTACA CACAAAAAGC ATACTTGCAT TATTTATAAT3660
AAAATTGCAT TCAGTGGCTT


SO TTTAAAAAAA ATGTTTGATT CAAAACTTTA ACATACTGAT3720
AAGTAAGAAA CAATTATAAT


TTCTTTACAT ACTCAAAACC AAGATAGAAA AAGGTGCTAT3780
CGTTCAACTT CAAAACATGT


TTCCTAGTAT TAAGGACTTT AATATAGCAA CAGACAAAAT3840
TATTGTTAAC ATGGATGTTA


CAGCTCAAAA GATTTATAAA AGATTTTAAC CTATTTTCTC3900
CCTTATTATC CACTGCTAAT


GTGGATGTAT GTTCAAACAC CTTTTAGTAT TGATAGGTTA3960
CATATGGCCA AAGGAATACA


;:


y p;_:
:K
v


l~q,g
' .


~, .~!. ~,. ~,7~. '~ ,u 1~ _ 1~
k .,.... : ~~hnl~vlW r ~~.,~'~ fyl~'t~~y ~ ' 1
4


CA 02459219 2004-03-17
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v''~ ~~.' ~~~ ~j~
~'~di i'('.u:x~;'~ f~ ,:'~
' f


, ~
. .~
i ~
~~~~.~~'


. ~, j
Lt'CJ~ thi


GTTTATAGCA AAACATGGGT ATGCTGTAGC TAACTTTATA4020
AAAGTGTAAT ATAACAATGT


AAAAAATTAT ATATCTGGGA GGATTTTTTG GTTGCCTAAA4DB0
GTGGCTATAG TTACTGATTT


TTTATTATGT AAGCAAAACC AATAAAAATT TAAGTTTTTT9140
TAACAACTAC CTTATTTTTC


ACTGTACAGA CACTAATTCA TTAAATACTA ATTGATTGTT4200
S TAAAAGAAAT ATAAATGTGA


CAAGTGGACA TTATTTATGT TAAATATACA ATTATCAAGC4260
AAGTATGAAG TTATTCAATT


AAAATGCCAC ATTTCTGGTC TCTGGG


Protein sequence 6 (SEQ ID N0:378)


Gene name: endothelia receptor type B
1
O


Unigene number: He.82002


Protein Accession #: NP 000106


Signal sequence: 1-27


Pfam domain: 7tm l [118-386]


Transmembrane domains: 100-122, 13B-160,
1 173-195, 221-243, 277-299, 325-347, 358-380
S


Cellular Localization: plasma membrane


1 11 21 31 41 51


MQPPPSLCGR ALVALVLACG LSRIWGEERG FPPDRATPLL60
QTAEIMTPPT KTLWPKGSNA


SLARSLAPAE VPKGDRTAGS PPRTISPPPC QGPIEIKETF120
ZO KYINTWSCL VFVLGIIGNS


TLLRIIYXNK CMRNGPNILI ASLALGDLLH IVIDIPINVY1B0
KLLAEDWPFG AEMCKLVPFI


QKASVGITVL SLCALSIDRY RAVASWSRIK GIGVPKWTAV240
EIVLIWWSV VLAVPEAIGP


DIITMDYKGS YLRICLLHPV QKTAFMQFYK TAKDWWLFSF300
YFCLPLAITA FFYTLMTCEM


LRKKSGMQIA LNDHLKQRRE VAKTVFCLVL VFALCWLPLH360
LSRILKLTLY NQNDPNRCEL


r~ LSFLLVLDYI GINMASLNSC INPIALYLVS KRFKNCFKSC420
GS LCCWCQSFEE KQSLEEKQSC
S SS


LKFKANDHGY DNFRSSNKY


DNA sequence 7 (SEQ ID N0:379)


Gene name: G protein-coupled receptor 34


Unigene number: He.29202
3
O


Probeset Accession #: N54926


Nucleic Acid Accession #: AF0396B6


Codlng sequence: 79-1224


1 11 21 31 41 51


3 AAAAACCTGA AGACATAAGA ACTACACATG AGGAATATGT60
S CATTTAGCAC TTTCACTTTT


TGATCTCCAC AGAAGACA_AT GAGAAGTCAT ACCATAACAA120
TGACGACAAC TTCAGTCAGC


AGCTGGCCTT ACTCCTCCCA CAGAATGCGC TTTATAACCA180 -
ATCATAGCGA CCAACCGCCA


_
CAAAACTTCT CAGCAACACC AAATGTTACT ACCTGTCCCA240
TGGATGAAAA ATTGCTATCT


ACTGTGTTAA CCACATCCTA CTCTGTTATT TTCATCGTGG300
4O GACTGGTTGG GAACATAATC
~


GCCCTGTATG TATTTCTGGG TAT2 360
~1CCGT AAAAGAAATT CCATTCAAAT TTATCTAGTT


AACGTAGCCA TTGCAGACCT CCTACTCATC TTCTGCGTCC420
CTTTCCGAAT CATGTATCAT


ATTAACCAAA ACAAGTGGAC ACTAGGTGTG ATTCTGTGCA4B0
AGGTTGTGGG AACACTGTTT


TATATGAACA TGTACATTAG CATTATTTTG CTTGGATTCA540
TCAGTTTGGA TCGCfATATA


AAAATTAATC GGTCTATACA GCAACGGAAG GCAATAACAA600
4S CCAAACAAAG TATTTATGTC


TGTTGTATAG TATGGATGGT TGCTCTTGGT GGATTCCTAA660
CTATGATTAT TTTAACACTT


AAGAAAGGAG GGCATAATTC CACAATGTGT TTCCATTACA720
GAGATAAGCA TAACGCAAAA


GGAGAAGCCA TTTTTAACTT CATTCTTGTG GTAATGTTCT780
GGCTAATTTT CTTACTAATA


ATCCTTTCAT ATATTAAGAT TGGGAAGAAT CTATTGAGGAB40
TTTCTAAAAG GAGGTCAAAA.


TTTCCTAATT CTGGTAAATA TGCCACTACA GCTCGTAACT900
SO CCTTTATTGT ACTTATCATT f
ATCATGCC TTTCG
TTC
T
T GTTTTGTTCC C
C
TCTAC


TTACTATA 0~
T ~
ATT '
A 4
AT ~
~~A '
~


AATGTATCAT CTTGCTACTG GAAAGAAATT GTTCACAAAAlb~
CCAATGAGAT b i
CIAAi~C; 6~ '~,. r
w !:


CTCTCATCTT TCAATAGTTG CTTAGATCCA GTCATGTATT1080
TCCTGATGTC CAGTAACATT


CGCAAAATAA TGTGCCAACT TCTTTTTAGA CGATTTCAAG1140
GTGAACCAAG TAGGAGTGAA


AGCACTTCAG AATTTAAACC AGGATACTCC CTGCATGATA120D
S CATCTGTGGC AGTGAAAATA
S


CAGTCTAGTT CTAAAAGTAC T_TGAGGTAAA CATACTAAAA1260
TGAATTATAT AATGCAGCCT


CTTAATTCTT TGAAGAACTA AAAAATTAGG AAACAAAGTT1320
CTAGCATTTA CAAAACTCAG


ATCTCAAAGC TCTGCTTGTA TTTGTGATAT TTCATTTGCT
TAACTGTAAA CCAT


Protein sequence 7 (SEQ ID N0:380)

x


r . ,, ,;~.;.,.j~S
~
t,,
Gene name: G protein-coupled receptor 34


~;
~ ,
Unigene number: He.29202
"'


Protein Accession #: AAD50531


Signal sequence: none found


Pfam domain: 7tm 1 [71-327]


~S Tranamembrane domains: 90-112, 126-148,
171-193, 217-239, 263-285


Cellular Localization: plasma membrane


1 11 21 31 41 51


MRSHTITMTT TSVSSWPYSS HRMRFITNHS DQPPQNFSAT60
7O PNVTTCPMDE KLLSTVLTTS


YSVIFIVGLV GNIIALYVFL GIHRKRNSIQ IYLLNVAIAD120
LLLIFCLPFR IMYHINQNKW


TLGVILCKVV GTLFYMNMYI SIILLGFISL DRYIKINRSI1B0
QQRKAITTKQ SIYVCCIVWM


VALGGFLTMI ILTLKXGGHN STMCFHYRDK HNAKGEAIFN240 .
FILVVMFWLI FLLIILSYIK


IGKNLLRISK RRSKFPNSGK YATTARNSFI VLIIFTICFV300
PYHAFRFIYI SSQLNVSSCY


WKEIVHKTNE IMLVLSSFNS C'LDPVMYFLM SSNIRKIMCQ360
LLFRRFQGEP SRSESTSEFK


7S PGYSLHDTSV AVKIQ9SSKS T


' DNA SEQUENCE B (9EQ ID N0:381)


Gene name: exostoses (multiple)-like 2


Unigene number: Hs.61152


$O Nucleic Acid Accession #: NM_001439


Coding sequence: 288-1280


' 1 11 21 31 41 51


CACTTTGCGG GCGGCACTTT TTCCAGGTTG TTAATCCAGC60
TAATGGAGAA GGATAGATGC


144 .

- '; S f;


CA 02459219 2004-03-17
<"'_r:.:'z'.~ . .


It~'~ u::i -;f '. ' '' ~,. i~'~:a~ i~:a'~ '
u~~.n , ~r~~:r-.
~N
',r~,,
~
~
.
...~
~c



'
tt,.~ W


ACGCTACTTG GTTTAGAAAA AAAAACAAAA ATGAGCAAAC120
GAGACGCCCC TTCCGTTTTA


TGATAACTAA GCTGCAGGGA AATAAATCGG CTGGCCCTAC180
TGCAATCTAC TGCACTCGAG


AAACATCACA GAAAATTCTT TGATTTATCT TAATAGTGAC240
AAGTGAGCCT GCTTCTGTCA


ATTACTGAAG CTATAAGGAG ATTTTTTAAA AATTAAACTT300
S CAACACAATG AGGTGTTGCC


w ~ ACATCTGCAA ACTTCCTGGG AGAGTAATGG GGATTCGAGT360
GCTTCGATTA TGTTTGGTGG


- TCATCCTCGT ATTATTACTG GTAGCTGGTG CTTTGAGTGCCTTACTTCCC420
AGTGTTAAAG


AAGACAAGAT GCTCATGTTG CGTAGGGAAA TAAAATCCCA480
GGGCAAGTCC ACCATGGACT


CCTTTACTCT CATAATGCAG ACGTACAACA GAACAGATCT540 ,
CTTATTGAAA CTTTTAAATC


ATTATCAGGC TGTACCAAAT CTGCACAAAG TGATTGTGGT600
1 O ATGGAACAAT ATTGGAGAGA


AGGCACCAGA TGAATTATGG AATTCTCTAG GGCCCCACCC660
TATCCGTGTG ATCTTCAAAC


AACAGACAGC AAACAGGATG AGAAATCGAC TCCAGGTCTT720
TCCTGAACTG GAAACCAATG


CAGTGTTGAT GGTAGATGAT GACACACTCA TCAGCACCCC780
AGACC2TGTT TTTGCfTTCT


CAGTTTGGCA GCAATTTCCT GATCAAATTG TAGGATTTGT840
TCCTAGAAAG CACGTCTCTA


CTTCATCAGG TATCTACAGT TATGGAAGTT TTGAAATGCA900
1 S AGCACCAGGG TCTGGAAATG


GTGACCAGTA CTCTATGGTG CTGATTGGAG CCTCATTCTT960
CAATAGCAAA TATCTTGAAT


TATTTCAGAG GCAACCTGCA GCTGTCCATG CTTTGATAGA1020,
TGATACTCAA AACTGTGATG


ATATTGCCAT GAATTTTATC ATTGCCAAGC ATATTGGCAA1080
GACTTCAGGG ATATTTGTGA


AGCCTGTAAA CATGGACAAT TTGGAAAAAG AAACCAACAG1140
TGGCTATTCT GGAATGTGGC


r~ ATCGAGCTGA GCACGCTCTG CAGAGGTCTT ATTGTATAAA1200
' TAAGCTTGTT AATATCTATG
" ~O


. ATAGCATGCC CTTAAGATAC TCCAACATTA TGATTTCCCA1260
GTTTGGTTTT CCATATGCCA


ACTACAAAAG AAAAATATAA AAGTAAAACA AACAAAAACA1320
AACCTGAAAA CTGCTTGGCA


TTTGAGTAGC TTCTCCATGC TATGTATTTT TTTAAGCAAC1380
ATCATGAATT TTATCTACTC


CAGAAGTCTC TACAATAGAA AHAAAAGTGC AGTGCTTCTA1440
GGATATAAAA TTCACATTAC


.~ TTTTGAAAGC CAAGAAGTTG GTCTTATCCA GTTAGGTCTT1500
S CTTATGAAGA GTTTTCATCC


...G AGGGATATAA CTCCTTGGTC AGTGATTTTA TTGTTTACAT1560
CCTGAGACTG TTCTACAGTT


TCTTTGACTC CTGGCATTTG CCTTAAGGAC CTATAGCAAG1620
CTGTTTCTAG GATCAGAAAC


TCAAGAGAGG CATTTCTCTG CTTTTTCACT AAAGGTCAGT1680
TGTTTTAATT TGAAACCTGA


AATGCCTCTT TAGCAAAGCC TGTGGTATGG GGTAAAGCCA1740
TGTAAGAAGA GAATAGTCTC


? AGTCACATAT GAAGAGGAAA ATTTGCAGCT GCCAGTGCTT1800
O TCCfTGTGGC CCTGCCAACC


J AGCTCTTCCA GGACGAACTC AGTCCAGCAT GGTTTTGATG1860
TAACCATCCA TGCfTTTATT


TTTGTTAAGT CTTTTGTGAC TGGGACAGTT AATTTTAGTA1920
GCTGAAGAAC GTCTAGTTGT


TTGCTTGATA TTTGTGAACA TTTACTGCAT GGATCACAAA1980
ACAATATACC CTGTATTTCT


TACACGCCAC TTATATGCAG CAAGGAGTAA ATGTGTTACT2040
AGATTCGGGT AGTGCATTTT


GTCACTGAAT CTGACCTTGA GAATGTACAT TAATTCTTAT2100
3S ATTTTACATA ATGTATGTGT


TGTTTAAGAA ATGTATAAAA AACCTGAAAA AAATGAGTAA2160
GAACTGGCAG AAGTTAAAAC


CCTTTGTATC AAAAGATCTT TATTGGTAGA GCACTGGTTA2220
TCTTCTGGAT ACTAAAAAGT


TGTATTACAA AGCCAAACAC TTGCATTCAC AACTTTAAAA2280
AAAGATCCAA GGAACTATTC


ATAATGATGA AATTTCAACT ACATACAAGG AGGAGAAAAT2340-
AAGAACCCAG TCATAACAGA


GGAATTCTAT AGGAGTCTGC ATCAATTCAT TCTTAAGGTT2400
4O GCCTACTCTC TGTTATGTGA


' ATTAGCGTCT GTGTTTCACC CATTGTCTGT GTTTAGTCCT2460
TGTTCACCAC TAAGGCAAGG


AATTCTTAAC TAGGCCTCTG TTTACCAACT TCTCTTTCTC2520
CTCCTTTCCC TCTTATTCCT


CCTTCTCCTC TTCCFTGTTA TATAATGCTA GTATATTCTC2580
AAAATTGCAA AGCTGTGAGA


. . ATATTAAAAT AATCATGGCT AATGTTCCAA TAATGAGGTC2640
TTTGTGCATT TAGTTCCGCA


TATGATGGTT TTTTTTTTAC ATTAAAGAGT ATATGTGTCT2700
4S TAATGCAGTC AGATTGTAAA


AAACAAAAAC AAAGAAACTA AGAATCTTAC TAAAAATCGA2760
TAATGTCAGT TATCTGTTTT


GTCCAATATT GGTAGTACTT TTTTGCCrCT TATGATTCCT2820
CTAGCAGATA AATAAAAGAA


ACTTTTGCCA TCC


Protein sequence 8 (SEQ ID N0:382)
SO


Gene name: exoetoses (multiple)-like 2


Unigene number: He.61152


Protein Accession #: NP_001430


Signal sequence: 1-38


Transmembrane domains: none found
S
S


Cellular Localization: plasma membrane


1 11 21 31 41 51


MRCCHICKLP GRVMGIRVLR LSLWILVLL LVAGALTALL 60
PSVKEDKMLM LRREIKSQGK


,C STMDSFTLIM QTYNRTDLLL KLLNHYQAVP NLHKVIVVWN120
O NIGEKAPDEL WNSLGPHPIP


v VIFKQQTANR MRNRLQVFPE LETNAVLMVD DDTLISTPDL180
VFAFSVWQQF PDQIVGFVPR


KHVSTSSGIY SYGSFEMQAP GSGNGDQYSM VLIGASPFNS240
KYLELFQRQP AAVHALIDDT


QNCDDIAMNF IIAKHIGKTS GIFVKPVNMD NLEKETNSGY300 ' ''~' "
SGMV7HRAEHA LQRSYCINKL


VDSMPLR YSNIMISQFG FPYANYKRKI


6S DNA SEQUENCE 9 ISEQ ID N0:383) '


Gene name: Homo sapiens growth differentiation'
factor 1 (GDF1)


Un3.Q~e number: Hs.92614


Probeset Accession #: AL120193


Nucleic Acid Accession #: NM
021267


70 ,
Coding se ezyce: 73-1125 '


1 ~~.i~w 21 . 31 41 51


ACGCGGGGCG CGCGGCTCCG TCGGCTACCG CGGGCGGGCG60
CAGGCGACGG GCACGGCGGG


CGAGCGGG~~6 GTATGGCGGC GGCGGGGCCC GCGGCGGGGC120
CGACGGGGCC CGAGCCCATG


7S CCCiAGCTFI'CG CGCAGCTAGT GCAGCGCGGC TGGGGCAGCG180
CGCTGGC~(ic GGCGCGGGGC


TGCACGGACT GCGGCTGGGG GC'fGGCGCGT CGCGGCCTGG240
CTGAGCACGCGCACCTGGCG


CCGCCCGAGC TGCTGCTGCT GGCGCTCGGC GCGCTGGGCT300
GGACCGCGCT GC~CTCCGCG


GCCACTGCGC GCCTCTTTCG GCCCCTGGCG AAGCGGTGCT360
GCCTCCAGCC CAGAGATGCC


GCCAAGATGC CCGAGAGCGC TTGGAAGTTT CTCTTCTACC420
SO TGGGCAGC'PG GAGCTACAGT


GCCTACCTGC TGTTTGGCAC CGACTACCCC TTCTTCCATG480
ACCCACCATC TGTCTTCTAC


GACTGGACGC CGGGCATGGC AGTGCCACGG GACATTGCAG540
CCGCCTACCT GCTCCAGGGA


AGCTTCTATG GCCACTCCAT CTACGCTACG CTATACATGG600
ACACCfGGCG CAAGGACTCG


GTGGTCATGC TGCTCCACCA CGTGGTCACT CTCATCCTCA660
TCGTCTCCTC CTACGCCTTC


CGGTACCACA ATGTGGGCAT CCTTGTGCTC TTCCfGCACG720
ATATCAGTGA CGTGCAGCTT


<:
14S
. .
.. ..~ ~. ~.....~~r.

CA 02459219 2004-03-17



~~~~:.
- ,..



- GAGTTCACCA AGCTCAACAT TTACFTCAAG TCCCGCGGCG780
GCTCCTACCA TCGGCTGCAT


-._ GCCTTGGCAG CAGACTTGGG CTGCCTCAGC TTCGGCTTCA840
GCTGGTTCTG GTTCCGCCTC


TACTGGTTCC CGCTCAAGGT CCTGTATGCC ACCAGTCACT900
GCAGTCTGCG CACGGTGCCT


GACATCCCCT TGTAGTTCTT GTTCAATGCG CTCCTGCTGC960
TGCTCACCCT TATGAACCTC


S TAGTGGTTCC TGTACATCGT GGCGTTTGCA GCCAAGGTGT1020
TGACAGGCCA GGTGCACGAG


CTGAAGGACC TGCGGGAGTA TGACACAGCC GAGGCCCAGA1080
GCCTGAAGCC CAGCAAAGCC


GAGAAGCCAC TGAGGAACGG CCTGGTGAAG GACAAGCGCT1140
TCTGAACCCC TCGGCCCCGC


CCCCGTGGAC CCGGCCCCAC CCCGAATACC CCGGCCACGC1200
TCCCCGTCCT TGGCCGCCCC


TCCACCCCCT CCAACTCTGC TCCTCTAGGG CCGCCGCCAC1260
CTCCCCTGGG ACCCCGCCCC


1 O CTCATCCTGC CTCCATTTCC CGGCCACGCC CCCCAGGACC1320
CCTGCCCCTC CGGGGACACC


GGCCCCGCCC TCAGCCCACT GGTCCCGGGC CGCCGCGGAC1380
CCTGCGCACT GTCTGGTCAT


CGCCTGGGAG GAAGATGCCA CCGCCGCAGC AAGGTCCCTG1440
CGGCCACCAC GTCCTCCTCC


TCCTGGCCCT GCTGCfGCCC TCGCTGCCCC TGACCCGCGC1500
CCCCGTGCCC CCAGGCCCAG


CCGCCGCCCT GCTCCAGGCT CTAGGACTGC GCGATGAGCC1560
CCAGG(iTGCC CCCAGGCTCC


I S GGCCGGTTCC CCCGGTCATG TGGCGCCTGT TTCGACGCCG1620
GGACCCCCAG GAGACCAGGT


CTGGCTCGCG GCGGACGTCC CCAGGGGTCA CCCTGCAACC1680
GTGCCACGTG GAGGAGCTGG


GGGTCGCCGG AAACATCGTG CGCCACATCC CGGACCGCGG1740
TGCGCCCACC CGGGCCTCGG


AGCCTGTCTC GGCCGCGGGG CATTGCCCTG AGTGGACAGT1800
CGTCTTCGAC CTGTCGGCTG


' TGGAACCCGC TGAGCGCCCG AGCCGGGCCC GCCTGGAGGT1860
GCGTTTCGCG GCGGCGGCGG


~0 CGGCAGCCCC GGAGGGCGGC TGGGAGCTGA GCGTGGCGCA1920
AGCGGGCCAG GGCGCGGGCG


CGGACCCCGG GCCGGTGCTG CTCCGCCAGT TGGTGCCCGC1980
CGTGGGGCCG CCAGTGCGCG


CGGAGCTGCT GGGCGCCGCT TGGGCTCGCA ACGCCTCATG2040
GCCGCGCAGC CTCCGCCTGG


CGCTGGCGCT ACGCCCCCGG GCCCCTGCCG CCTGCGCGCG2100
CCtGGCCGAG GCCTCGCTGC


TGCTGGTGAC CCTCGACCCG CGCCTGTGCC ACCCCCTGGC2160
ZS CCGGCCGCGG CGCGACGCCG


AACCCGTGTT GGGCGGCGGC CCCGGGGGCG CTTGTCGCGC2220
GCGGCGGCTG TACGTGAGCT


TCCGCGAGGT GGGCTGGCAC CGCTGGGTCA TCGCGCCGCG2280
CGGCTTCCTG GCCAACTACT


GCCAGGGTCA GTGCGCGCTG CCCGTCGCGC TGTCGGGGTC2340
CGGGGGGCCG CCGGCGCTCA


ACCACGCTGT GCfGCGCGCG CTCATGCACG CGGCCGCCCC2400
GGGAGCCGCC GACCTGCCCT


GCTGCGTGCC CGCGCGCCTG TCGCCCATCT CCGTGCTCTT2460
3O CTTTGACAAC AGCGACAACG


TGGTGCTGCG GCAGTATGAG GACATGGTGG TGGACGAGTG
CGGCTGCCGC TAACCCGGGG


Protein sequence 9 (S&Q ID N0:384)
Gene name: Homo sapiens growth differentiation factor 1 (GDF1)
Unigene number: Hs.92614
3 S Protein Accession #: NP 067090
Signal sequence: none found
Transmembrane domalris: 106-128, 148-169, 184-206, 244-266, 285-307
Cellular Localization: plasma membrane
40 11 21 31 41 51
MAAAGPAAGP TGPEPMPSYA QLVQRGWGSA LAAARGCTDC GWGLARRGLA EHAHLAPPEL 60
LLLALGALGW TALRSAATAR LFRPLAKRCC LQPRDAAKMP ESAWKFLFYL GSWSYSAYLL 120
FGTDYPFFHD PPSVFYDWTP GMAVPRDIAA AYLLQGSFYG HSIYATLY1~ TWRKDSVVML 180
LHHVVTLILI VSSYAFRYHN VGILVLFLHD ISDVQLEFTK LNIYFKSRGG SYHRLHALAA 240
4S DLGCLSFGFS WFWFRLYWFP LKVLYATSHC SLRTVPDIPF YFFFNALLLL LTLDffILYWFL 300
YIVAPAAKVL TGQVHELKDL REYDTAEAQS LKPSKAEKPL RNGLVKDKRF
DNA SEQUENCE 10 (SEQ ID N0:385)


Gene name: epidermal growth factor receptorleukemia
(avian erythroblastic


SO Unigene number: Hs.77432


Nucleic Acid Accession #= NM_005228


Coding sequence: 187-3819


1 11 21 31 41 51


S GCCGCGCTGC GCCGGAGTCC CGAGCTAGCC CCGGCGCCGC60
S CGCCGCCCAG ACCGGACGAC


AGGCCACCTC GTCGGCGTCC GCCCGAGTCC CCGCCTCGCC120
GCCAACGCCA CAACCACCGC


GCACGGCCCC CTGACTCCGT CCAGTATTGA TCGGGAGAGC180
CGGAGCGAGC TCTTCGGGGA


GCAGCGATGC GACCCTCCGG GACGGCCGGG GCAGCGCTCC240
TGGCGCTGGT GGCTGCGCTC


TGCCCGGCGA GTCGGGCTCT GGAGGAAAAG AAAGTTTGCC300
AAGGCACGAG TAACAAGCTC


6O ACGCAGTTGG GCACTTTTGA AGATCATTTT CTCAGCCTCC360
AGAGGATGTT CAATAACTGT


GAGGTGGTCC TTGGGAATTT GGAAATTACC TATGTGCAGA420
GGAATTATGA TCTTTCCTTC


TTAAAGACCA TCCAGGAGGT GGCTGGTTAT GTCCTCATTG480
CCCTCAACAC AGTGGAGCGA


ATTCCTTTGG AAAACCTGCA GATCATCAGA GGAAATATGT540
ACTACGAAAA TTCCTATGCC


TTAGCAGTCf TATCTAACTA TGATGCAAAT AAAACCGGAC600
TGAAGGAGCT GCCCATGAGA


6S AATTTACAGG AAATCCTGCA TGGCGCCGTG CGGTTCAGCA660
ACAACCCTGC CCTGTGCAAC


GTGGAGAGCA TCCAGTGGCG GGACATAGTC AGCAGTGACT720
TTCTCAGCAA CATGTCGATG


GACTTCCAGA ACCACCTGGG CAGCTGCCAA AAGTGTGATC780
CAAGCTGTCC CAATGGGAGC


TGCTGGGGTG CAGGAGAGGA GAACTGCCAG AAACTGACCA840
AAATCATCTG TGCCCAGCAG


TGCTCCGGGC GCTGCCGTGG CAAGTCCCCC AGTGAC'fGGT900
GCCACAACCA GTGTGCTGCA


7O GGCTGCACAG GCCCCCGGGA GAGCGACTGC CTGGTCTGCC960
GCAAATTCCG AGACGAAGCC


ACGTGCAAGG ACACCTGCCC CCCACTCATG CTCTACAACC1020
CCACCACGTA CCAGATGGAT


GTGAACCCCG AGGGCAAATA CAGCTTTGGT GCCACCTGCG1080
TGAAGAAGTG TCCCCGTAAT


TATGTGGTGA CAGATCACGG CTCGTGCGTC CGAGCCTGTG1140
GGGCCGACAG CTATGAGATG


GAGGAAGACG GCGTCCGCAA GTGTAAGAAG TGCGAAGGGC1200
CTTGCCGCAA AGTGTGTAAC


7S GGAATAGGTA TTGGTGAATT TAAAGACTCA CTCTCCATAA1260
ATGCTACGAA,TATTAAACAC
~


ATTTAGGGGT 1320
TTCAAAAACT GCACCTCCAT CAGTGGCGAT CTCCACATCC
TGCCGGTGGC


GACTCCTTCA CACATACTCC TCCTCTGGAT CCACAGGAAC1380
TGGATATTCT GAAAACCGTA


AAGGAAATCA CAGGGTTTTT GCTGATTCAG GCTTGGCCTG1440
AAAACAGGAC GGACCTCCAT


GCCTTTGAGA ACCTAGAAAT CATACGCGGC AGGACCAAGC2500
AACATGGTCA GTTTTCTCTT


SO GCAGTCGTCA GCCTGAACAT AACATCCTTG GGATTACGCT1560
CCCTCAAGGA GATAAGTGAT


GGAGATGTGA TAATTTCAGG AAACAAAAAT TTGTGCTATG1620
CAAATACAAT AAACTGGAAA


AAACTGTTTG GGACCTCCGG TCAGAAAACC AAAATTATAA1680
GCAACAGAGG TGAAAACAGC


TGCAAGGCCA CAGGCCAGGT CTGCCATGCC TTGTGCTCCC1740
CCGAGGGCTG CTGGGGCCCG


GAGCCCAGGG ACTGCGTCTC TTGCCGGAAT GTCAGCCGAG1800
GCAGGGAATG CGTGGACAAG


146


CA 02459219 2004-03-17
,..~., , . ~~,~ .r~'..'~' ~.~~' ~"f' .. ~3~~n
'~ A:r~'' ~"ie~~. Y"t. ..li.i~ ~~~~ T I
~


TGCAAGCTTC TGGAGGGTGA GCCAAGGGAG TTTGTGGAGA~''6
ACTCTGAGTG CATACAGTGC 18


CACCCAGAGT GCCTGCCTCA GGCCATGAAC ATCACCTGCA192
CAGGACGGGG ACCAGACAAC


TGTATCCAGT GTGCCCACTA CATTGACGGC CCCCACTGCG198
TCAAGACCTG CCCGGCAGGA


GTCATGGGAG AAAACAACAC CCTGGTCTGG AAGTACGCAG204
ACGCCGGCCA TGTGTGCCAC


S CTGTGCCATC CAAACTGCAC CTACGGATGC ACTGGGCCAG2100
GTCTTGAAGG CTGTCCAACG


AATGGGCCCA AGATCCCGTC CATCGCCACS GGGATGGTGG2160
GGGCCCTCCT GTTGCTGCTG


GTGGTGGCCC TGGGGATCGG CCTCPTCATG CGAAGGCGCC2220
ACATCGTTCG GAAGCGCACG


CTGCGGAGGC TGCTGCAGGA GAGGGAGCTT GTGGAGCCTC2280
TTACACCCAG TGGAGAAGCT


CCCAACCAAG CTCTCTTGAG GATCTTGAAG GAAACTGAF1T2340
TCAAAAAGAT CAAAGTGCTG


1 GGCTCCGGTG CGTTCGGCAC GGTGTATAAG GGACTCTGGA2400
0 TCCCAGAAGG TGAGAAAGTT


AAAATTCCCG TCGCTATCAA GGAATTAAGA GAAGCAACAT2460
CTCCGAAAGC CAACAAGGAA


ATCCTCGATG AAGCCTACGT GATGGCCAGC GTGGACAACC2520
CCCACGTGTG CCGCCTGCFG


GGCATCTGCC TCACCTCCAC CGTGCAACTC ATCACGCAGC2580
TCATGCCCTT CGGCTGCCTC


CTGGACTATG TCCGGGAACA CAAAGACAAT ATTGGCTCCC2640
AGTACCTGCT CAACTGGTGT


Z GTGCAGATCG CAAAGGGCAT GAACTACTTG GAGGACCGTC2700
S GCTTGGTGCA CCGCGACCTG


GCAGCCAGGA ACGTACTGGT GAAAACACCG CAGCATGTCA2760
AGATCACAGA TTTTGGGCTG


GCCAAACTGC TGGGTGCGGA AGAGAAAGAA TACCATGCAG2820
AAGGAGGCAA AGTGCCTATC


AAGTGGATGG CATTGGAATC AATTTTACAC AGAATCTATA2880
CCCACCAGAG TGATGTCTGG


AGCTACGGGG TGACCGTTTG GGAGTTGATG ACCTTTGGAT2940
CCAAGCCATA TGACGGAATC


ZO CCTGCCAGCG AGATCTCCTC CATCCTGGAG AAAGGAGAAC3000
GCCTCCCTCA GCCACCCATA ,
,


TGTACCATCG ATGTCTACAT GATCATGGTC AAGTGCTGGA3060
TGATAGACGC AGATAGTCGC '


CCAAAGTTCC GTGAGTTGAT CATCGAATTC TCCAAAATGG3120
CCCGAGACCC CCAGCGCTAC


CTTGTCATTC AGGGGGATGA AAGAATGCAT TTGCCAAGTC3180
CTACAGACTC CAACTTCTAC


CGTGCCCTGA TGGATGAAGA AGACATGGAC GACGTGGTGG3240
ATGCCGACGA GTACCTCATC


ZS CCACAGCAGG GCTTCTTCAG CAGCCCCTCC ACGTCACGGA3300
CTCCCCTCCT GAGCTCTCTG


AGTGCAACCA GCAACAATTC CACCGTGGCT TGCATTGATA3360
GAAATGGGCT GCAAAGCTGT


CCCATCAAGG AAGACAGCTT CTTGCAGCGA TACAGCTCAG3420
ACCCCACAGG CGCCTTGACT


GAGGACAGCA TAGACGACAC CTTCCTCCCA GTGCCTGAAT3480
ACATAAACCA GTCCGTTCCC


AAAAGGCCCG CTGGGTCTGT GCAGAATCCT GTCTATCACA3540
ATCAGCCTCT GAACCCCGCG


30 CCCAGCAGAG ACCCACACTA CCAGGACCCC CACAGCACTG3600
CAGTGGGCAA CCCCGAGTAT


CTCAACACTG TCCAGCCCAC CTGTGTCAAC AGCACATTCG3660
ACAGCCCTGC CCACTGGGCC


CAGAAAGGCA GCCACCAAAT TAGCCTGGAC AACCCTGACT3720
ACCAGCAGGA CTTCTTTCCC


AAGGAAGCCA AGCCAAATGG CATCTTTAAG GGCTCCACAG3780
CTGAAAATGC AGAATACCTA


AGGGTCGCGC CACAAAGCAG TGAATTTATT GGAGCATGAC3840
CACGGAGGAT AGTATGAGCC


2 CTAAAAATCC AGACTCTTTC GATACCCAGG ACCAAGCCAC3900
J AGCAGGTCCT CCATCCCAAC
S


AGCCATGCCC GCATTAGCTC TTAGACCCAC AGACTGGTTT3960
TGCAACGTTT ACACCGACTA


~t GCCAGGAAGT ACTTCCACCT CGGGCACATT TTGGGAAGTT4020
GCATTCCTTT GTCTTCAAAC


TGTGAAGCAT TTACAGAAAC GCATCCAGCA AGAATATTGT4080
CCCTTTGAGC AGAAATTTAT


CTTTCAAAGA GGTATATTTG AAAAAAAAAA AAAAAGTATA4140
4O TGTGAGGATT TTTATTGATT


GGGGATCTTG GAGTTTTTCA TTGTCGCTAT TGATTTTTAC4200
TTCAATGGGC TCTTCCAACA


AGGAAGAAGC TTGCTGGTAG CACTTGCTAC CCTGAGTTCA4260
TCCAGGCCCA ACTGTGAGCA


_
AGGAGCACAA GCCACAAGTC TTCCAGAGGA TGCTTGATTC4320
CAGTGGTTCT GCTTCAAGGC


TTCCACTGCA AAACACTAAA GATCCAAGAA GGCCTTCATG4380
GCCCCAGCAG GCCGGATCGG


TACTGTATCA AGTCATGGCA GGTAGAGTAG GATAAGCCAC4440
TCTGTCCCTT CCTGGGCAAA


4S GAAGAAACGG AGGGGATGAA TTCTTCCTTA GACTTACTTT4500
TGTAAAAATG TCCCCACGGT '


ACTTACTCCC CACTGATGGA CCAGTGGTTT CCAGTCATGA4560
GCGTTAGACT GACTTG2tTG


TCTTCCATTC CATTGTTTTG AAACTCAGTA TGCCGCCCCT4620
GTCTTGCTGT CATGAAATCA


GCAAGAGAGG ATGACACATC AAATAATAAC TCGGATTCCA4680
GCCCACATTG GATTCATCAG


CATTTGGACC AATAGCCCAC AGCTGAGAAT GTGGAATACC4740
TAAGGATAAC ACCGCTTTTG


SO TTCTCGCAAA AACGTATCTC CTAATTTGAG GCTCAGATGA4800
AATGCATCAG GTCCTTTGGG


GCATAGATCA GAAGACTACA AAAATGAAGC TGCTCfGAAA4860
TCTCCCTTAG CCATCACCCC


AACCCCCCAA AATTAGTTTG TGTTACTTAT GGAAGATAGT4920
TTTCTCCTTT TACTTCACTT


CAAAAGCTTT TTACTCAAAG AGTATATGTT CCCTCCAGGT4980
CAGCTGCCCC CAAACCCCCT'


CCTTACGCTT TGTCACACAA AAAGTGTCTC TGCCTTGAGT5040
CATCTATTCA AGCAGTTACA


S GCTCTGGCCA CAACAGGGCA TTTTACAGGT GCGAATGACA5100
S GTAGCATTAT GAGTAGTGTG


AATTCAGGTA GTAAATATGA AACTAGGGTT TGAAATTGAT5160
AATGCTTTCA CAACATTTGC


AGATGTTTTA GAAGGAAAAA AGTTCCTTCC TAAAATAATT5220
TCTCTACAAT TGGAAGATTG


GAAGATTCAG CTAGTTAGGA GCCCATTTTT TCCTAATCTG5280
TGTGTGCCCT GTAACCTGAC


~ TGGTTAACAG CAGTCCTTTG TAAACAGTGT TTTAAACTCT5340
O CCTAGTCAAT ATCCACCCCA


l) TCCAATTTAT CAAGGAAGAA ATGGTTCAGA AAATATTTTC5400
AGCCTACAGT TATGTTCAGT


CACACACACA TACAAAATGT TCCTTTTGCT TTTAAAGTAA5460
TTTTTGACTC CCAGATCAGT


CAGAGCCCCT ACAGCATTGT TAAGAAAGTA TTTGATTTTT5520
GTCTCAATGA AAATAAAACT


ATATTCATTT CC


VS Protein sequence 10 (SEQ ID N0:386]


Gene name: epidermal growth factor receptorleukemia
(avian erythroblaatic


Unigene number: Hs.77432


Protein Accession #: NP_005219


Signal sequence: 1-27


.
70 Pfam domain: Recep L domain (57-190, 372-492]


Tranamembrane domains: 646-668


1 11 . 21 31 41 51


MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ60
LGTFEDHFLS LQRMFNtICEV


7S VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP120
LENLQIIRGN MYYENSYALA


VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE180
SIQWRDIVSS DFLSNMSNll7F


QNHLGSCQKC DPSCPNGSCV7 GAGEENCQKL TKIICAQQCS240
GRCRGKSPSD CCHNQCAAGC


TGPRBBDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN300
PEGKYSFGAT CVKKCPRNYV


VTDHGSCVRA CGADSYEMEE DGVRKCKKCB GPCRKVC~1GI360
GIGEFKDSLS INATNIKHFK


SO NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE420
ITGFLLIQAW PENRTDLHAF


ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD480
VIISGNKNLC YANTINWKKL


FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP540
RDCVSCRNVS RGRECVDKCK


LLBGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI600
QCAHYIDGPH CVKTCPAGVM


GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCPTNG660
PKIPSIATGM VGALLLLLW



147


CA 02459219 2004-03-17
.. ~..I~,~ ', ' ~..,i~ ~,"I. Is "(i ; ...-,..~ :H::~ :).::~ y,~'"w..'a d-'~
~(. ~ r, n, y ....p ~ '(' ~'~
~~a... .~'' H'
ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEApN QALLRILKET EFKKIKVLGS 720
GAFGTVYKGL WIPEGEKVKI PVAIKELREA TSPKANKEIL DEAYVMASVD NPHVCRLLGi x.780
CLTSTVQLIT QLMPFGCLLD YVRfiHKDNIG SQYLLNWCVQ IAICGMNSCLED RRLVHRDLAA 840
RNVLVKTPQH VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY 900
S GVTVWELMTP GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC WMIDADSRPK 960
FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA LNmEEDMDDV VDADEYLIPQ 1020
QGFFSSPSTS RTPLLSSLSA TSNNSTVACI DRNGLQSCPI KEDSFLQRYS SDPTGALTED 1080
SIDDTFLPVp EYINQSVPKR PAGSVQNPVY HNQPLNPApS RDPHYQDPHS TAVGNPEYLN 1140
TVQPTCVNST FDSPAHWAQK GSHQISLDNP DYQQDPFPKE AKPNGIFKGS TAENAEYLRV 1200
1 O APQSSEFIGA
DNA sequence 11 (SEQ ID N0:387)


Gene name: claudin 5 (transmembrane protein
deleted in velocardiofacial syndrome)


1 LTnigene number: Hs-110903
S


1 Probeset Accession #: AW245805


Nucleic Acid Accession #: NM
003277


_
Coding sequence: 121-777


1 11 21 31 41 51
w ~


G a.
AGGGGACTGG GGCCAAGAGC CGGGAGCGC ,~:
~
~
.
x


G GGCGCAAAGG CACCAGGGCC CGCCCAGGGC 6

~
~
w


GCCGCGCAGC ACGGCCTTGG GGGTTCTGCG GGCCTTCGGG120
TGCGCGTCTC GCCTCTAGCC


ATGGGGTCCG CAGCGTTGGA GATCCTGGGC CTGGTGCTGT180
GCCTGGTGGG CTGGGGGGGT


.~ CTGATCCTGG CGTGCGGGCT GCCCATGTGG CAGGTGACCG240
GS CCTTCCTGGA CCACAACATC


GTGACGGCGC AGACCACCTG GAAGGGCCTG TGGATGTCGT300
GCGTGGPGCA GAGCACCGGG


CACATGCAGT GCAAAGTGTA CGACTCGGTG CTGGCTCTGA360
GCACCGAGGT GCAGGCGGCG


CGGGCGCTCA CCGTGAGCGC CGTGCTGCTG GCGTTCGTTG420
CGCTCTTCGT GACCCTGGCG


GGCGCGCAGT GCACCACCTG CGTGGCCCCG GGCCCGGCCA480
AGGCGCGTGT GGCCCTCACG


GGAGGCGTGC TCTACCTGTT TTGCGGGCTG CTGGCGCTCG540
3O TGCCACTCTG CTGGTTCGCC


AACATTGTCG TCCGCGAGTT TTACGACCCG TCTGTGCCCG600
TGTCGCAGAA GTACGAGCTG


GGCGCAGCGC TGTACATCGG CTGGGCGGCC ACCGCGCTGC660
TCATGGTAGG CGGCTGCGTC


TTGTGCTGCG GCGCCTGGGT CTGCACCGGC CGTCCCGACC720
TCAGCTTCCC CGTGAAGTAC


TCAGCGCCGC GGCGGCCCAC GGCCACCGGC GACTACGACA780
AGAAGAACTA CGTCTGAGGG


CGCTGGGCAC GGCCGGGCCC CTCCTGCCAG CCACGCCTGC840
3 GAGGCGTTGG ATAAGCCTGG
S


GGAGCCCCGC ATGGACCGCG GCTTCCGCCG GGTAGCGCGG900
CGCGCAGGCT CCTCGGAACG


TCCGGCTCTG CGCCCCGACG CGGCTCCTGG ATCCGCTCCT960
GCCTGCGCCC GCAGCTGACC


TTCTCCTGCC ACTAGCCCGG CCC'TGCCCTT AACAGACGGA1020
ATGAAGTTTC CTTTTCTGTG


_
CGCGGCGCTG TTTCCATAGG CAGAGCGGGT GTCAGACTGA 1080
GGATTTCGCT TCCCCTCCAA


GACGCTGGGC; GTCTTGGCTG CTGCCTTACT TCCCAGAGGC1140
TCCTGCTGAC TTCGGAGGGG


CGGATGCAGA GCCCGGGGCC CCCACCGGAA GATGTGTACA1200
GCTGGTCTTT ACTCCATCGG


CAGGCCCGAG CCCAGGGACC AGTGACTTGG CCTGGACCTC1260
CCGGTCTCAC TCCAGCATCT


CCCCAGGCAA GGCTTGTGGG CACCGGAGCT TGAGAGAGGG1320
CGGGAGTGGG AAGGCTAAGA


ATCTGCTTAG


4S Protein sequence 1l (SEQ ID N0:388)


Gene name: claudin 5 (transmembrane proteinfacial syndrome)
deleted in velocardio


Unigene number: Hs.110903


Protein Accession #: NP_003268


Signal sequence: none found
S
O


Pfam domain: PMP22 Claudin [4-181)


Transmembzane domains: 5-27, 74-96, 123-145,
164-186


' Cellular Localization: plasma membrane


1 11 21 31 41 51


S MGSAALEILG LVLCLVGWGG LILACGLPMW QVTAFLDHNI60
S VTAQTTWKGL WMSCWQSTG


HMQCKVYDSV LALSTEVQAA RALTVSAVLL AFVALFVTLA120
GAQCTTCVAP GPAKARVALT


GGVLYLFCGL LALVPLCWFA NIWREFYDP 9VPVSQKYEL 180
GAALYIGWAA TALLMVGGCL


LCCGAWCTG RPDLSFPVKY SAPRRPTATG DYDKKNYV


v0 DNA sequence 12 (SEQ ID N0:389)


Gene name: vascular endothelial junction-associated
molecule


Unigene number: Hs.54650


Probeset Accession #: AA410345


< Nucleic Acid Accession #: AF255910
S


V Coding sequence: 241-1137 .


1 11 21 31 ' 41' "' ~ 51


..
TTACCATTGT GTTGGGCTGC GAGAAGACGA CAGAAGGGGG 60
ACCCGCCTCT TGGCAGCCAG


CTGAGAAGGC GCCCCGGGGA GGGGGAAACT GACATCCCAT120
70 CTAGAGCCGT CCCTCCTCTT


CCTCCCCTCC CGACTCTCTG CTCCTTTCCC GCCCCAGAAG180
TTCAAGGGCC CCCGGCCTCC


TGCGCTCCTG CCGCCGGGAC CCTCGACCTC CTCAGAGCAG240
CCGGCTGCCG CCCCGGGAAG


ATGGCGAGGA GGAGCCGCCA CCGCCTCCTC CTGC:GGTGC300
TGCGCTACCT- GGTGGTCGCC


CTGGGCTATC ATAAGGCCTA TGGGTTTTCT GCCCCAAAAG360
ACCAACAGGT AGTCACAGCA


GTAGAGTACC AAGAGGCTAT TTTAGCCTGC AAAACCCCAA420
7S AGAAGACTGT TTCCTCCAGA
TAGA
G
A


T 480
GT
G
AGAAACTGGG TCGGAGTGTC TCCTTTGTCT ACTATCAACA
GACTCTTCAA


GGTGATTTTA AAAATCGAGC TGAGATGATA GATTTCAATA540
TCCGGATCAA AAATGTGACA


AGAAGTGATG CGGGGAAATA TCGTTGTGAA GTTAGTGCCC600
CATCTGAGCA AGGCCAAAAC


CTGGAAGAGG ATACAGTCAC TCTGGAAGTA TTAGTGGCTC660
CAGCAGTTCC ATCATGTGAA


p GTACCCTCTT CTGCTCTGAG TGGAACTGTG GTAGAGCTAC720
O GATGTCAAGA CAAAGAAGGG


O AATCCAGCTC CTGAATACAC ATGGTTTAAG GATGGCATCC780
GTTTGCTAGA AAATCCCAGA


CTTGGCTCCC AAAGCACCAA CAGGTCATAC ACAATGAATA840
CAAAAACTGG AACTCTGCAA


TTTAATACTG TTTCCAAACT GGACACTGGA GAATATTCCT900
GTGAAGCCCG CAATTCTGTT


GGATATCGCA GGTGTCCTGG GAAACGAATG CAAGTAGATG960
ATCTCAACAT AAGTGGCATC


ATAGCAGCCG TAGTAGTTGT GGCC'fTAGTG ATTTCCGTTT1020
GTGGCCTTGG TGTATGCTAT


1


;-..i-~.
-- " CA 02459219 2004-03-17
y.4~j~.. ~~ ~(~~ _ '~ ~, 3 fytt ~~', ~T y'k ~,. ~ ~' ~,' f'~f~~. t
a.. ,
i~ '~ 7ev~~.~t.
GCTCAGAGGA AAGGCTACTT TTCAAAAGAA ACCTCCTTCC AGAAGAGTAA TTCTTCATCT 1080
AAAGCCACGA CAATGAGTGA AAATGATTTC AAGCACACAA AATCCTTTAT AATT_TAAAGA 1140
CTCCACTTTA GAGATACACC AAAGCCACCG TTGTTACACA AGTTATTAAA CTATTATAAA 1200
ACTCTGCTTT GTCCGACATT TGCAAAGAGG TACACGAGGA AATGGAATTG GTATTTCATT 1260
S TTAATTTTCA TGACTACTAA CTCACCTGAA CTTGCTATTT TAAAMAAATA GTTCTGTCGA 1320
CACCTAAAAT ATAATCTGGC TTCTTGTGTC TGGACTAAGT TAAAAGAATT AAAATACTTT 1380
GTAATGTCAA AAAAAAA
Protein 6equence 12 (SEQ ID N0:390)


1 O Gene name: vascular endothelial junction-associated
molecule


Unxgene number: Hs.54650


Protein Accession #: AAF81223


Signal sequence: 1-22


Igc2 domain: 41-116, 146-221


1 S Transmembrane domains: 239-261


Cellular Localization: plasma membrane


1 11 21 31 41 51


MARRSRHRLL LLLLRYLWA LGYHKAYGFS APKDQQWTA 60
VEYQEAILAC KTPKKTVSSR


20 LEWKKLGRSV SFWYQQTLQ GDPXNRAEMI DFNIRIKNVT 120
RSDAGKYRCE VSAPSEQGQN


LEEDTVTLEV LVAPAVPSCE VPSSALSGTV VELRCQDKEG180
NPAPEYTWFK DGIRLLENPR


LGSQSTNSSY TMNTKTGTL FNTVSKLDTG EYSCEARNSV 240
GYRRCPGKRM QVDDLNISGI


IAAVWVALV ISVCGLGVCY AQRKGYFSKE TSFQKSNSSS
KATTMSENDF KHTKSFII


2S DNA sequence 13 (SEQ ID N0:391)


Gene name: solute carrier family 11 (proton-coupled
divalent metal ion


Unxgene number: Hs.182611


Probeset Accession #: D50402


Nucleic Acxd Accession #: NM 000578


30 Coding sequence: 1-1653


1 11 21 31 41 51


'; ATGACAGGTG ACAAGGGTCC CCAAAGGCTA AGCGGGTCCA60
GCTATGGTTC CATCTCCAGC


? CCGACCAGCC CGACCAGCCC AGGGCCACAG CAAGCACGTC120
3 S CCAGAGAGAC CTACCTGAGT 180
GAGAAGATCC CCATCCCAGA CACAAAACCG GGCACCTTCA
GGCTGCGGAA GCTATGGGCC


TTCACGGGGC CTGGCTTCCT CATGAGCATT GCTTTCCTGG240
ACCCAGGAAA CATCGAGTCA


GATCTTCAGC TNGGNCCNGT GGCGGGATTC AAACTTCTCT300
GGGTGCTGCT CTGGGCCACC


GTGTTGGGCT TGCTCEGCCA GCGACTGGCT GCACGTCTGG360 -
GCGTGGTGAC AGGCAAGGAC


TTGGGCGAGG TCTGCCATCT CTACTACCCT AAGGTGCCCC420
GCACCGTCCT CTGGCTGACC


4O ATCGAGCTAG CCATTGTGGG CTCCGACATG CAGGAAGTCA480
TCGGCACGGC CATTGCATTC


AATCTGCTCT CAGCTGGACG AATCCCIICTC TGGGGTGGCG540
TCCTCATCAC CATCGTGGAC


ACCTTCTTCT TCCTCTTCCT CGATAACTAC GGGCTGCGGA600
AGCTGGAAGC TTTTTTTGGA


CrCCTTATAA CCATTATGGC CTTGACCTTT GGCTATGAGT660
ATGTGGTGGC GCGTCCTGAG


CAGGGAGCGC TTCTTCGGGG CCTGTTCCTG CCCTCGTGCC720
CGGGCTGCGG CCACCCCGAG


4S CTGCTGCAGG CGGTGGGCAT TGTTGGCGCC ATCATCATGC780
CCCACAACAT CTACCTGCAC


TCGGCCCTGG TCAAGTCTCG AGAGATAGAC CGGGCCCGCC840
GAGTCGACAT CAGAGAAGCC


AACATGTACT TCCTGATTGA GGCCACCATC GCCCTGTCCG900
TCTCCTTTAT CATCAACCTC


TTTGTCATGG CTGCATTTGG GCAGGCCTTC TACCAGAAAA960
CCAAGCAGGC TGCGTTCAAC


ATCTGTGCCA ACAGCAGCCT CCACGACTAC GCTAAGATCT1020
TCCCCATGAA CAACGCCACC


SO GTGGCCGTGG ACATTTACCA GGGGGGCGTG ATCCTGGGCT1080
GCCTGTTCGG CCCCGCGGCC


CTCTACATCT GGGCCATAGG TCTCCTGGCG GCTGGGCAGA1140
GCTCCACCAT GACGGGCACC


TACGCGGGAC AGTTCGTGAT GGAGGGCTTC CrGAGGCTGC1200
GGTGGTCAAG CTTCGCCCGT


GTCCTCCTCA CCCGCTCCTG CGCCATCCTG CCCACCGTGC1260
TCGTGGCTGT CTTCCGGGAC


CTGAGGGACT TGTCGGGCCT CAATGATCTG CTCAACGTGC1320
TGCAGAGCCT GCTGCTCCCG


SS GTTGCCGTGC TGCCCATCCT CACGTTCACC AGCATGCCCA1380
CCCTCATGCA GGAGTTTGCC


AATGGCCTGC TGAACAAGGT CGTCACCTCT TCCATCATGG1440
TGCTAGTCTG CACCATCAAC


CTCTACTTCG TGGTCAGCTA TCTGCCCAGC CTGCCCCACC1500
CTGCCTACTT CGGCCTTGCA


GCCTTGCTGG CCGCAGCCTA CCTGGGCCTC AGCACCTACC1560
TGGTCTGGAC CTGTTGCCTT


GCCCACGGAG CCACCTTTCT GGCCCACAGC TCCCACCACC1620
ACTTCCTGTA TGGGCTCCTT
GACC A
AAAGGGGA GACCTCrGGC TAG
A


GAAG
G
C


Protein sequence 13 (SEQ ID N0:392)


Gene name: solute carrier family 11 (Proton-coupledion transporters), member
divalent metal 1


Unigene number: Ha.182611


t Protein Accession #: NP_000569
VS


Signal sequence: none found '


Pfam domain: Nramp [78-4631


Transmembrane domains: 58-80, 88-110, 159-181,
195-217, 284-306, 349-379, 394-416, 432-454,
468-490, 501-523


Cellular Localization: plasma membrane


~7 1 1l 21 31 41 51
/O


MTGDKGPQRL SGSSYGSISS PTSPTSPGPQ QAPPRETYLS60
EKIPIPDTKP GTFRLRKLWA


FTGPGFLMSI AFLDPGNIES DLQLGPVAGF KLLWVLLWAT120
VLGLLCQRLA ARLGVVTGKD


LGEVCHLYYP KVPRTVLWLT IELAIVGSDM QEVIGTAIAF180
NLLSAGRIPL WGGVLITIVD


~7 TFFFLFLDNY GLRKLEAFFG LLITIMALTF GYfiYWARPE240
/S QGALLRGLFL PSCPGCGHPE


LLQAVGIVGA IIMPHNIYLH SALVKSREID RARRVDIREA300
NMYFLIEATI ALSVSFIINL


FVMAAFGQAF YQKTKQAAFN ICANSSLHDY AKIFPMNNAT360
VAVDIYQGGV ILGCLFGPAA


LYIWAIGLLA AGQSSTMTGT YAGQFVMEGF LRLRW95FAR420
VLLTRSCAIL PTVLVAVFRD


LRDLSGLNDL LNVLQSLLLP VAVLPILTFT SMPTLMQEFA480
NGLLNKWTS SIMVLVCTIN


SO LYFWSYLPS LPHPAYFGLA ALLAAAYLGL STYLVWTCCL 540
AHGATFLAHS SHHHFLYGLL


EEDHKGETSG


DNA sequence 14 (SEQ ID N0:393) ,
Gene name: solute carrier family 7 (cationic amino acid transporter, y+
149
'1t~ x. ~n?~~'f.1 k. n'1, 7T %~.


CA 02459219 2004-03-17
~i~ y=." .,,'i., ' "~~' ~~.~y(t ~~. ~~ .f~~yt ~;k .. _~
~ II '~ ;~,~ -
E ~';~L'~
r
~


, . '~
;; , ~
~ .~
,,~,.
F ., .;



Unigene number: Hs.1846D1


Probeset Accession #: AP104032


Nucleic Acid Accession #: NM_003486


Coding sequence: 53-1576
S


1 1l 21 31 41 51


GCTCGCTGGG CCGCTGCTCC CGGGTGTCCC AGGCCCGGCC60
GGTGCGCAGA GC_ATGGCGGG


TGCGGGCCCG AAGCGGCGCG CGCTAGCGGC GCCGGCGGCC120
GAGGAGAAGG AAGAGGCGCG


GGAGAAGATG CTGGCCGCCA AGAGCGCGGA CGGCTCGGCG180
1 O CCGGCAGGCG AGGGCGAGGG


CGTGACCCTG CAGCGGAACA TCACGCTGCT CAACGGCGTG240
GCCATCATCG TGGGGACCAT


TATCGGCTCG GGCATCTTCG TGACGCCCAC GGGCGTGCTC300
AAGGAGGCAG GCTCGCCGGG


GCTGGCGCTG GTGGTGTGGG CCGCGTGCGG CGTCTTCTCC360
ATCGTGGGCG CGCTCTGCTA


CGCGGAGCTC GGCACCACCA TCTCCAAATC GGGCGGCGAC420
TACGCCTACA TGCTGGAGGT


CTACGGCTCG CTGCCCGCCT TCCTCAAGCT CTGGATCGAG480
I S CTGCTCATCA TCCGGCCTTC


ATCGCAGTAC ATCGTGGCCC TGGTCTTCGC CACCTACCTG540
CTCAAGCCGC TCTTCCCCAC


CTGCCCGGTG CCCGAGGAGG CAGCCAAGCT CGTGGCCTGC600
CTGTGCGTGC TGCTGCTCAC


GGCCGTGAAC TGCTACAGCG TGAAGGCCGC CACCCGGGTC660
CAGGATGCCT TTGCCGCCGC


CAAGCTCCTG GCCCTGGCCC TGATCATCCT GCTGGGCTTC720
GTCCAGATCG GAAAGGGTGA


~ TGTGTCCAAT CTAGATCCCA AGTTCTCATT TGAAGGCACC780
O AAAGTGGATG TGGGGAACAT


G TGTGCTGGCA TTATACAGCG GCCTCTTTGC CTATGGAGGA840
TGGAATTACT TGAATTTCGT


CACAGAGGAA ATGATCAACC CCTACAGAAA CCTGCCCCTG900
GCCATCATCA TCTCCCTGCC


CATCGTGACG CTGGTGTACG TGCTGACCAA CCTGGCCTAC960
TTCACCACCC TGTCCACCGA


GCAGATGCTG TCGTCCGAGG CCGTGGCCGT GGACTTCGGG1020
AACTATCACC TGGGCGTCAT


~ GTCCTGGATC ATCCCCGTCT TCGTGGGCCT GTCCTGCTTT.GGCTCCGTCA1080
S ATGGGTCCCT


G GTTCACATCC TCCAGGCTCT TCTTCGTGGG GTCCCGGGAA1140
GGCCACCTGC CCTCCATCCf


CfCCATGATC CACCCACAGC TCCTCACCCC CGTGCCGTCC1200
CTCGTGTTCA CGTGTGTGAT


GACGCTGCTC TACGCCTTCT CCAAGGACAT CTTCTCCGTC1260
ATCAACTTCT TCAGCTTGTT


CAACTGGCTC TGCGTGGCCC TGGCCATCAT CGGCATGATC1320 r
TGGCTGCGCC ACAGAAAGCC


.~ TGAGCTTGAG CGGCCCATCA AGGTGAACCT GGCCCTGCCT1380
. GTGTTCTTCA TCCTGGCCTG
O


J CCTCTTCCTG ATCGCCGTCT CCTTCTGGAA GACACCCGTG1440
GAGTGTGGCA TCGGCTTCAC


CATCATCCTC AGCGGGCTGC CCGTCTACTT CTTC1:GGGTC1500
TGGTGGAAAA ACAAGCCCAA


GTGGCTCCTC CAGGGCATCT TCTCCACGAC CGTCCTGTGT1560
CAGAAGCTCA TGCAGGTGGT


, CCCCCAGGAG ACATAGCCAG GAGGCCGAGT GGCTGCCGGA
GGAGCATGC


~3 S Protein sequence 14 (SEQ ID N0:394)


Gene name: solute carrier family 7 (cationic
ammo acid transporter, y+


Unigene number: Hs.184601


Protein Accession #: NP_003477 - -


A Pfam domain: as permeases [46-481)
s
O


1' Tranemembrane domains: 52-74, 82-104, 120-142,200-222, 275-297,
145-167, 169-191, 237-259, 323-345,
371-393,


398-419, 430-452, 455-476


Cellular Localization: plasma membrane


1 11 21 31 41 51


4S MAGAGPKRRA LAAPAAEEKE EAREKMLAAK SADGSAPAGE60
GEGVTLQRNI TLLNGVAIIV


GTIIGSGIFV TPTGVLKEAG SPGLALVVWA ACGVFSIVGA120
LCYAELGTTI SKSGGDYAYM


LEVYGSLPAF LKLWIELLII RPSSQYIVAL VFATYLLKPL180
FPTCPVpEEA AKLVACLCVL


LLTAVNCYSV KAATRVQDAF AAAKLLALAL IILLGFVQIG240
KGDVSNLDPK FSFEGTKLDV


GNIVLALYSG LFAYGGWNYL NFVTEEMINP YRNLPLAIII300
S O SLPIVTLVYV LTNLAYFTTL


STEQMLSSEA VAVDFGNYHL GVMSWIIPVF VGLSCFGSVN360
GSLFTSSRLF FVGSREGHLP


SILSMIHPQL LTPVPSLVFT CVMTLLYAFS KDIFSVINFF420
SFFNWLCVAL AIIGMIWLRH


RKPELERPIK VNLALPVFFI LACLFLIAVS FWKTPVECGI480
GFTIILSGLP VYFFGVWWKN


KPKWLLQGIF STTVLCQKLM QWPQET


S S DNA sequence 15 (SEQ ID N0:395)


Gene name: Glutamate receptor subunit


Unigene number: Hs.249141


Nucleic Acid Accession #: 540369


Coding sequence: 1-2943
60 1 11
1


21 31 41 5


_ATGCCGGCTG AGCTGCTGCT GCTGCTGATT GTTGCCTTCG60
CCAGCCCCAG CTGCCAGGTG


CTCTCATCAC TGCGCATGGC TGCAATCCTG GATGATCAGA120
CAGTGTGTGG CCGCGGTGAG


g CGTCTGGCCT TGGCCTTGGC CCGGGAGCAG ATCAACGGGA180
TCATCGAGGT CCCAGCCAAG


'~~ GCCCGAGTGG AAGTAGACAT CTTTGAGCTG CAGCGGGACA240 ,
GCCAGTACGA GACCACGGAC


ACCATGTGTC AGATCTTACC CAAAGGGGTT GTGTCTGTCC300
TTGGGCCCTC CTCTAGCCCA


GCATCTGCCT CCACCGTGAG CCATATCTGT GGAGAGAAGG360
AGATCCCCCA CATCAAGGTG


GGTCCCGAGG AGACACCCCG CCTTCAGTAC CTTCGCTTCG420
CGTCTGTCAG CCTGTACCCC


AGTAACGAGG ACGTCAGCTT GGCGGTCTCC CGAATCCTCA480
AGTCCTTCAA CTACCCCTCG


7O GCCAGCCTCA TCTGCGCCAA GGCTGAGTGC CTGCTGCGAT540
TGGAGGAACT GGTGCGTGGC


TTCCTCATCT CCAAGGAGAC GCTGTCAGTG AGGATGTTGG600
ACGACAGCCG GGACCCCACA


' CCACTGCTCA AGGAGATCCG TGATGACAAG GTGTCCACCA660
TCATCATCGA CGCCAACGCC


TCCATCTCCC ACCTCATCCT CCGTAAGGCC TCGGAACTGG720
GAATGACCTC AGCGTTTTAC


AAGTACATCC TCACCACCAT GGACTTCCCC ATCCTGCATC780
7S TGGACGGTAT TGTGGAGGAC


TCCTCCAACA TCCTGGGGTT CTCCATGTTC AACACGTCCC840
ACCCCTTCTA CCCfGAGTTT


GTCCGCAGCC TCAACATGTC CTGGAGGGAG AACTGTGAAG900
CCAGCACCTA CCTGGGCCCT


GCGCTGTCAG CCGCCCTGAT GTTTGACGCC GTGCACGTGG960
TGGTGAGCGC TGTCCGAGAG


CTGAACCGCA GCCAGGAGAT CGGTGTGAAG CCTCTGGCCT1020
GTACATCGGC CAACATTTGG


CCCCACGGGA CCAGCCTCAT GAACTACCTG CGCATGGTAG1080
, AGTATGATGG.:GCTGACCGGG


$O CGGGTCGAGT TCAACAGCAA AGGGCAGAGA ACCAACTACA1140
CCCTGCC;CAT CCTAGAAAAG


TCCCGGCAGG GCCACCGTGA GATTGGGGTG TGGTACTCTA1200
ACCGCACCCT GGCCATGAAT


GCCACCACCC TGGACATCAA CCTGTCGCAG ACACTGGCCA1260
ACAAGACCCT GGTGGTCACA


ACCATCCTGG AGAACCCATA CGTCATGCGC CGGCCCAACT1320
TCCAGGGCCT GTCGGGGAAC


GAACGCTTCG AGGGCTTCTG CGTGGACATG CTGCGGGAGC1380
TGGCCGAGCT GCTGCCGTTC



150
, . .,,. ~'

S F,... ~. ~. . . .., ; . . _ - , . . .. :. ' . . _. _.,.,. , .s_,~
,.:,.
'_ t _:
,',_..


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~ y
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~~ r ;t 1l- ~ ~
w.
~
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w.Jt
'
~
Rr

'~r~
.
~
1



_ . ' U~ ~ _


_ CCGTACCGCC TGCGGTTGGT GGAGGATGGG CTGTACGGGG1440
CGCCCGAGCC CAACGGCTCC


TGGACGGGCA TGGTTGGCGA GCTCATCAAC CGGAAGGCAG1500
ACCTGGCTGT GGCCGCCTTC


ACCATCACAG CTGAGCGGGA GAAGGTCATC GACTTTTCCA1560
AGCCCTTTAT GACCCTGGGG


ATCAGCATCC TCTACCGAGT GCACATGGGC CGCAAGCCTG1620
S GCTACTTCTC CTTCCTGGAC


CCCTTCTCCC CTGCTGTGTG GCTCTTCATG CTTCTTGCCT1680
ACCTGGCTGT CAGCTGCGTC


CTGTTTCTGG CTGCCAGGCT GAGCCCCTAT GAGTGGTATA'ACCCACACCC1740
ATGCCTGCGG


GCACGCCCCC ACATCCTGGA GAACCAGTAC ACGCTGGGCA1800
ACAGCCTGTG GTTTCCCGTG


GGGGGCTTCA TGCAGCAGGG CTCGGAGATC ATGCCCCGGG1860
CGCTGTCCAC GCGCTGTGTC


AGCGGAGTCT GGTGGGCCTT CACCTTGATC ATCATCTCCT1920
I O CCTACACGGC CAACCTGGCC


GCCTTCCTCA CCGTGCAGCG CATGGAGGTG CCTGTGGAGT1980
CGGCCGATGA CCTGGCAGAT


CAGACCAACA TCGAGTATGG CACCATCCAC GCCGGCTCCA2040
CCATGACCTT CTTCCAGAAT


TCACGGTACC AAACGTACCA GCGCATGTGG AACTACATGC2100
AGTCGAAGCA GCCCAGCGTG


TTCGTCAAGA GCACAGAAGA GGGCATTGCC GCCGTCCTCA2160
ACTCCCGCTA CGCCTTCCTG


CTCGAGTCCA CCATGAACGA ATACCACCGG CGCCTCAACT2220
I S GCAACCfCAC CCAGATCGGG


GGACTCCTCG ACACCAAGGG CTACGGCATT GGCATGCCGC2280
TGGGCTCCCC GTTCCGGGAT


_ GAGATCACAC TGGCCATCCT GCAGGTTCAG GAGAACAACC2340
GGCTGGAGAT CCTGAAGCGC


AAGTGGTGGG AGGGGGGCCG GTGCCCCAAG GAGGAGGACC2400
ATCGAGCTAA AGGTTTGGGC


ATGGAGAACA TTGGTGGCAT T'TTTATCGTG CTCATCTGTG2460
GCCTCATCAT TGCTGTCTTC


_... GTGGCGGTCA TGGAATTCAT ATGGTCCACA CGGAGGTCAG2520
CTGAGTCCGA GGAGGTGTCG


GTGTGCCAGG AGATGCTGCA GGAGCTGCGC CACGCCGTTT2580
CTTGCCGCAA GACGTCGCGT


- ' TCCCGCCGGC GCCGACGCCC GGGCGGCCCG AGCCGGGCCC2640
TGCTGTCACT GCGCGCGGTC


CGCGAGATGC GCCTCAGCAA CGGCAAGCTC TACTCGGCCG2700
GCGCGGGCGG GGATGCGGGC


AGCGCGCACG GGGGCCCGCA GCGCCTCCTG GACGACCCGG2760
GGCCCCCCAG CGGAGCCCGA


CCCGCCGCCC CCACCCCCTG CACCCACGTG CGCGTCTGCC2820
AGGAGTGCCG GCGCATCCAG


~7 GCGCTGCGGG CCTCGGGGGC CGGCGCGCCT CCGCGTGGCC2880
GS TGGGCGTCCC CGCCGAAGCC


ACCAGCCCGC CCCGGCCGCG GCCTGGCCCC GCCGGCCCCC2940
GGGAGCTGGC GGAGCACGAG


T GA


Protein sequence 15 (SEQ ID N0:396)


30 Gene name. Glutamate receptor subunit


Unigene number: Hs.249141


Protein Accession #: AAB22591


!. Signal sequence: 1-27


t Pam domain: ANP receptor [343-400];PHPe
domain (416-785, 799-838]


~3S Transmembrane domains: 297-3i9, 544-566,
624-646, 803-825


Cellular Localization: plasma membrane


1 11 21 31 , 41 S1


MPAELLLLLI VAFASPSCQV LSSLRMAAIL DDQTVCGRGE60
RLALALAREQ INGIIEVPAK


,~ ARVEVDIFEL QRDSQYETTD TMCQILPKGV VSVLGPSSSP120
'tO ASASTVSHIC GEKEIPHIKV


GPEETPRLQY LRFASVSLYP SNEDVSLAVS RILKSFNYPS180
ASLICAKAEC LLRL$fiLVRG


FLISKETLSV RMLDDSRDPT PLLKEIRDDK VSTIIIDANA240
SISHLILRKA SELGMTSAFY


KYILTTMDFP ILHLDGIVED SSNILGFSMF NTSHPPYPEF300
VRSLNMSWRE NCEASTYLGP


ALSAALMFDA VHVWSAVRE LNRSQEIGVK PLALZ'SANIW360
PHGTSLMNYL RMVEYDGLTG


~ RVEFNSKGQR TNYTLRILSK SRQGHREIGV WYSNRTLAMN420
't5 ATTLDINLSQ TLANKTLVVT


i 980
TILENPYVMR RPNFQGLSGN ERFEGFCVDM LRELAELLPF
PYRLRLVEDG LYGAPEPNGS


WTGMVGELIN RKADLAVAAF TITAEREKVI DFSKPFMTLG540
ISILYRVHMG RKPGYFSFLD


PFSPAVWLFM LLAYLAVSCV LFLAARLSPY EWYNPHPCLR600
ARPHILENQY TLGNSLWFPV


GGFMQQGSEI MPRALSTRCV SGVWWAFTLI IISSYTANLA'
AFLTVQRMEV PV$SADDLAD 660


S O QTNIEYGTIH AGSTMTFFQN SRYQTYQRMW NYMQSKQPSV720
FVKSTEEGIA AVLNSRYAFL


LESTMNEYHR RLNCNLTQIG GLLDTKGYGI GMPLGSPFRD780
EITLAILQLQ ENNRLEILKR


KWWfiGGRCPK EEDHRAKGLG MENIGGIFIV LICGLIIAVP840
VAVMEFZWST RRSAESSEVS


VCQEMLQELR HAVSCRKTSR SRRRRRPGGP SRALLSLRAV900
REMRLSNGKL YSAGAGGDAG


SAHGGPQRLL DDPGPPSGAR PAAPTPCTHV RVCQECRRIQ960
ALRA$GAGAP PRGLGVPAEA


S S TSPPRPRFGP AGPRELAEHE


DNA sequence 16 (SEQ ID N0:397)


Gene name: adenosine A3 receptor


'' Unigene number: Hs.258


~ Probeset Accession #: NM_000677


Nucleic Acid Accession #: NM_000677


Coding sequence: 768-1724


1 11 21 31 41 51


ATCTTTGCTG CAAAGGCTGG GTATCGGCTG TGCTCAGCAA60
AGCGTCAACT CGTGCAAGAA


CrTAGCAGGA ATAGTTCTGG CTAAGGTTAG GAGGCTGCCA120
CCAAAGTCTC TTTTTTGTTC


CTCTGCTTCT CCCGTTTGCC TCCTTATCAT GAGATCTTTT180
TGCTAAGCTG GCAGAAAGAT


TGCATAGTCA GTGCTTCCAG CTCTGCTCCC ACCTGATCCT240
GCACTGTCCT CTGGTCCCTG


AATGAATGAA CTCTGATACC CAATCTTGTC TCGAGCCTTC300
TCTATGCCAC TCATGGCTCC


7O TCTTCTGCTC TTTCCATCTT TTTGCTGAGA GTTCTGAGCT360
CTGTACTTCC TCTTGGCCCA


TCTCACTTCC TGAAACACCC CTGAAGAGGG TTGCTTATCT420
TGATGGAACT CAAAAAGCCA


AAAAGCTGCA GGCAGAGGCG TTGAGGACAT CTGTTTGGGG480
AACTAAGAGC AGCAGCACTT


TCAGATTCAG TCCATATAGA GCTGTCCTAC AGCATTCTGG540
AAACTTGAGG ATGTGCGGTG


CATAAAGGGG CTGGAAGTGA CCCACCfGTG ATGAGCCCTT600
TCTAAGGAGA AGGGTTTCCA


7S AGAGATCACC CCACCAGAAA AGGGTAGGAA TGAGCAAGTT660
GGGAATTTTA GACTGTCACT


GCACATGGAC CTCTGGGAAG ACGTCTGGCG AGAGCTAGGC720
CCACTGGCCC TACAGACGGA


TCTTGCTGGC TCACCTGTCC CTGTGGAGGT TCCCCTGGGA780
AGGCAAG_ATG CCCAACAACA


GCACTGCTCT GTCATTGGCC AATGTTACCT ACATCACCAT840
GGAAATTTTC ATTGGACTCT


GCGCCATAGT GGGCAACGTG CTGGTCATCT GCGTGGTCAA900
GCTGAACCCC AGCCTGCAGA


SO CCACCACCTT CTATTTCATT GTCTCTCTAG CCCTGGCTGA960
CATTGCTGTT GGGGTGCTGG


TCATGCCTTT GGCCATTGTT GTCAGCCTGG GCATCACAAT1020
CCACTTCTAC AGCTGCCTTT


TTATGACTTG CCTACTGCTT ATCTTTACCC ACGCCTCCAT1080
CATGTCCTTG'CTGGCCATCG


CTGTGGACCG ATACTTGCGG GTCAAGCTTA CCGTCAGATA1140
CAAGAGGGTC ACCACTCACA


GAAGAATATG GCTGGCCCTG GGCCTTTGCT GGCTGGTGTC1200
ATTCCTGGTG GGATTGACCC


r_
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t
s
r
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y
,
.
H


_. .. ., _ _:~. ~
z ~y ~~ a'~,


i.. ;"",..:


.
Vi


CCATGTTTGG CTGGAACATG AAACTGACCT CAGAGTACCA1260
CAGAAATGTC ACCTTCCTTT


CATGCCAATT TGTTTCCGTC ATGAGAATGG ACTACATGGT1320
ATACTTCAGC TTCCTCACCT


GGATTTTCAT CCCCCTGGTT GTCATGTGCG CCATCTATCT1380
TGACATCTTT TACATCATTC


GGAACAAACT CAGTCTGAAC TTATGTAACT CCAAAGAGAC1440
S AGGTGCATTT TATGGACGGG


AGTTCAAGAC GGCTAAGTCC TTGTTTCTGG TTCTTTTCTT1500s~
GTTTGCTCfG TCATGGCTGC


CTTTATCTAT CATCAACTGC ATCATCTACT TTAATGGTGA156D
GGTACCACAG CTTGTGCTGT


ACATGGGCAT CCTGCTGTCC CATGCCAACT CCATGATGAA1620
CCCTATCGTC TATGCCTATA


AAATAAAGAA GTTCAAGGAA ACCTACC'TTT TGATCCTCAA1680
AGCCTGTGTG GTCTGCCATC


CCTCTGATTC TTTGGACACA AGCATTGAGA AGAATTCTGA1740
1 G_TAGTTATCC ATCAGAGATG
0


ACTCTGTCTC ATTGACCTTC AGATTCCCCA TCAACAAACA1800
CTTGAGGGCC TGTATGCCTG


GGCCAAGGGA TTTTTACATC CTTGATTACT TCCACTGAGG1860
TGGGAGCATC TCCAGTGCTC


CCCAATTATA TCTCCCCCAC TCCACTACTC TCTTCCTCCA1920
CTTCATTTTT CCTTTGTCCT


TTCTCTGTAA TTCAGTGTTT TGGAGGCCTG ACTTGGGGAC1980
AACGTATTAT TGATATTATT


GTCTGTTTTC CTTCTTCCCA ATAGAAGAAT AAGTCATGGA2040
I GCCTGAAGGG TGCCTAGTTG
S


ACTTACTGAC AAAAGGCTCT AGTTGGGCTG AArATGTGTG2100
TGGTGGTGAC TCATTTCCAT


GCCATTGTGG AATTGAGCAG AGAACCTGCT CTCGGAGGAT2160
GCCTAGAAGA TGTTGGGAAC


AGAAGAAATA AACTGAGTTT AAGGGGGACT TAAAC'TGCTG2220
AATTCACCTG TGGATGTTTT


TGAGTAAATA AAAGCTAATA G



20 Protein sequence 16 (SEQ ID N0:398)
Gene name: adenosine A3 receptor
Unigene number: Hs.258
Protein Accession #: NP_000668
Signal sequence: none found
2S Pfam domain: 7tm 1 [29-282]
Transmembrane domains: 12-34, 50-72, 86-108, 120-150, 179-201, 229-251
Cellular Localization: plasma membrane
1 11 21 31 41 51
3O MPNNSTALSL ANVTYITMEI FIGLCAIVGN VLVICWKLN PSLQTTTFYF IVSLALADIA 60
VGVLVMPLAI WSLGITIHF YSCLFMTCLL LIFTtIASIMS LLAIAVDRYL RVKLTVRYKR 120
VTTHRRIWLA LGLCWLVSFL VGLTPMFGWN MKLTSEYHRN VTFLSCQFVS VMRMDYMVYF 180
SFLTWIFIPL VVMCAIYLDI FYIIRNKLSL NLSNSKETGA FYGREFKTAK SLFLVLFLFA 240
LSWLPLSIIN CIIYFNGEVP QLVLYMGILL SHANStR~INPI VYAYKIKKFK ETYLLILKAC 30D
3S WCHPSDSLD TSIESQISE
DNA sequence 17 tSEQ ID N0:399)


Gene name: glypican 1 - -


Unigene number: Hs.2699


n Probeset Accession #: X542'32
4O


Nucleic Acid Accession #: NM 002081


Coding sequence: 222-1898


1 1l 21 31 41 51


4S GGCTGCCCGA GCGAGCGTTC GGACCTCGCA CCCCGCGCGC60
CCCGCGCCGC CGCCGCCGCC


GGCTTTTGTT GTCTCCGCCT CCTCGGCCGC CGCCGCCTCT120
GGACCGCGAG CC'GCGCGCGC


CGGGACCTTG GCTCTGCCCT TCGCGGGCGG GAACTGCGCA180 ;"a ~ /t!*v~%
GGACCCGGCC AGGATCCGAG


AGAGGCGCGG GCGGGTGGCC GGGGGCGCCG CCGGCCCCGC240 ~;l~y }~,t"
CATGGAGCTC CGGGCCCGAG


GCTGGTGGCT GCTATGTGCG GCCGCAGCGC TGGTCGCCTG300 ,
CGCCCGCGGG GACCCGGCCA


SO GCAAGAGCCG GAGCTGCGGC GAGGTCCGCC AGATCTACGG360
AGCCAAGGGC TTCAGCCTGA


GCGACGTGCC CCAGGCGGAG ATCTCGGGTG AGCACCTGCG420
GATCTGTCCC CAGGGCTACA


CCTGCTGCAC CAGCGAGATG GAGGAGAACC TGGCCAACCG480
CAGCCATGCC GAGCTGGAGA


CCGCGCTCCG GGACAGCAGC CGCGTCCTGC AGGCCATGCT540
TGCCACCCAG CTGCGCAGCT


TCGATGACCA CTTCCAGCAC CTGG'TGAACG ACTCGGAGCG600,
GACGCTGCAG GCCACCTTCC


S CCGGCGCCTT CGGAGAGCTG TACACGCAGA ACGCGAGGGC660
S CTTCCGGGAC CTGTACTCAG


AGCTGCGCCT GTACTACCGC GGTGCCAACC TGCACCTGGA720
GGAGACGCTG GCCGAGTTCT


GGGCCCGCCT GCTCGAGCGC CTCTTCAAGC AGCTGCACCC780
CCAGCTGCTG CTGCCTGATG


ACTACCTGGA CTGCCTGGGC AAGCAGGCCG AGGCGCTGCG840
GCCCTTCGGG GAGGCCCCGA


GAGAGCTGCG CCTGCGGGCC ACCCGTGCCT TCGTGGCTGC900
TCGCTCCTTT GTGCAGGGCC


TGGGCGTGGC CAGCGACGTG GTCCGGAAAG TGGCTCAGGT960
CCCCCTGGGC CCGGAGTGCT


CGAGAGCTGT CATGAAGCTG GTCTACTGTG CTCACTGCCT1020
GGGAGTCCCC GGCGCCAGGC


CCTGCCCTGA CTATTGCCGA AATGTGCTCA AGGGCTGCCT1080
TGCCAACCAG GCCGACCTGG


ACGCCGAGTG GAGGAACCTC CTGGACTCCA TGGTGCTCAT1140
CACCGACAAG TTCTGGGGTA


CATCGGGTGT GGAGAGTGTC ATCGGCAGCG TGCACACGTG1200
GCTGGCGGAG GCCATCAACG


6 CCCTCCAGGA CAACAGGGAC ACGCTCACGG CCAAGGTCAT1260 .
S CCAGGGCTGC GGGAACCCCA


AGGTCAACCC CCAGGGCCCT GGGCCTGAGG AGAAGCGGCG1320
CCGGGGCAAG CTGGCCCCGC


GGGAGAGGCC ACCTTCAGGC ACGCTGGAGA AGCTGGTCTC1380
TGAAGCCAAG GCCCAGCTCC


GCGACGTCCA GGACTTCTGG ATCAGCCTCC CAGGGACACT1490
GTGCAGTGAG AAGATGGCCC


TGAGCACTGC CAGTGATGAC CGCTGCTGGA ACGGGATGGC1500
CAGAGGCCGG TACCTCCCCG


7O AGGTCATGGG TGACGGCCTG GCCAACCAGA TCAACAACCC1560
CGAGGTGGAG GTGGACATCA


CCAAGCCGGA CATGACCATC CGGCAGCAGA TCATGCAGCT1620
GAAGATCATG ACCAACCGGC


TGCGCAGCGC CTACAACGGC AACGACGTGG ACTTCCAGGA1680
CGCCAGTGAC GACGGCAGCG


GCTCGGGCAG CGGTGATGGC TGTCTGGATG ACCTGTGCGG1740
CCGGAAGGTC AGCAGGAAGA


GCTCCAGCTC CCGGACGCCC TTGACCCATG CCCTCCCAGG1800
CCTGTCAGAG CAGGAAGGAC


7S AGAAGACCTC GGCTGCCAGC TGCCCCCAGC CCCGGACCTT1860
CCTCCTGCCC CTCCTCCTCT


TCCTGGCCCT TACAGTAGCC AGGCCCCGGT GGCGG_TAACT1920
GCCCCAAGGC CCCAGGGACA


GAGGCCAAGG ACTGACTTTG CCAAAAATAC AACACAGACG1980
ATATTTAATT CACCTCAGCC


TGGAGAGGCC TGGGGTGGGA CAGGGAGGGC CGGCGGCTCT2040
GAGCAGGGGC AGGCGCAGAG


GTCCCAGCCC CAGGCCTGGC CTCGCCTGCC TTTCTGCCTT2100
TTAATTTTGT ATGAGGTCCT


S CAGGTCAGCT GGGAGCCAGT GTGCCCAAAA GCCATGTATT2160
O TCAGGGACCT CAGGGGCACC


TCCGGCTGCC TAGCCCTCCC CCCAGCTCCC TGCACCGCCG2220
CAGAAGCAGC CCCTCGAGGC


CTACAGAGGA GGCCTCAAAG CAACCCGCTG GAGCCCACAG2280
CGAGCCTGTG CCTTCCTCCC


CGCCTCCTCC CACTGGGACT CCCAGCAGAG CCCACCAGCC..2340
AGCCCTGGCC CACCCCCCAG;


CCTCCAGAGA AGCCCCGCAC GGGCTGTCTG GGTGTCCGCC2400
ATCCAGGGTC TGGCA~AGCC


.__. 1S2 ~ .




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TCTGAGATGA TGCATGATGC CCTCCCGTCA GCGCAGGCTG2460
CAGAGCCCGG CCCCACCTCC


CTGCGCCCfT GAGGGGCCCC AGCGTCTGCA GGGTGACGCC2520
TGAGACAGCA CCACTGCTGA


GGAGTCTGAG GACTGTCCTC CCACAGACCC TGCAGTGAGG2580
GGCCCfCCAT GCGCAGATGA


GGGGCCACTG ACCCACCTGC GCTTCTGCTG GAGGAGGGGA2640
AGCTGGGCCC AAAGGCCCAG


S GGAGGCAGCG TGGGCTCTGC CAATGTGGGC TGCCCCTCGC2700
ACACAGGGCT CACAGGGCAG


GCCTTGCTGG GGTCCAGGGC TGTTGGAGGA CCCCGAGGGC2760
TGAGGAGCAG CCAGGACCCG


CCTGCTCCCA TCCTCACCCA GATCAGGAAC CAGGGCC'TCC2820
CTGTTCACGG TGACACAGGT


CAGGGCTCAG AGTGACCCTC GGCTGTCACC TGCTCACAGG2880
GATGCTGGTG GCTGGTGAGA


CCCCGCACTG CACACGGGAA TGCCTAGGTC CCTTCCCGAC2940
CCAGCCAGCT GCACTGCAGG


1 GCACGGGGAC CrGGATAGTT AAGGGCTTTT CCAAACATGC3000
O ATCCATTTAC TGACACTTCC


TGTCCTTGTT CATGGAGAGC TGTTCGCTCC TCCCAGATGG3060
CTTCGGAGGC CCGCAGGGCC


CACCTTGGAC CCTGGTGACC TCCTGTCACT CACTGAGGCC3120
ATCAGGGCCC TGCCCCAGGC


CTGGACGGGC CCTCCTTCCC TCCTGTGCCC CAGCTGCCAG3180
GTGGCCCTGG GGAGGGGTGG


TGTGGTGTTG GGAAGGGGTC CTGCAGGGGG AGGAGGACTT3240
GGAGGGTCTG GGGGCAGCTG


1 TCCTGAACCG ACTGACCCTG AGGAGGCCGC TTAGTGCTGC3300
S TTTGCTTTTC ATCACCGTCC


CGCACAGTGG ACGGAGGTCC CCGGTTGCTG GTCAGGTCCC3360
CATGGCTTGT TCTCTGGAAC


CTGACTTTAG ATGTTTTGGG ATCAGGAGCC CCCAACACAG3420
GCAAGTCCAC CCCATAATAA


CCCTGCCAGT GCCAGGGTGG GCTGGGGACT CTGGCACAGT3480
GATGCCGGGC GCCAGGACAG


CAGCACTCCC GCTGCACACA GACGGCCTAG GGGTGGCGCT3540
CAGACCCCAC CCTACGCTCA


ZO TCTCTGGAAG GGGCAGCCCT GAGTGGTCAC TGGTCAGGGC3600
AGTGGCCAAG CCTGCTGTGT


CCTTCCTCCA CAAGGTCCCC CCACCGCTCA GTGTCAGCGG3660
GTGACGTGTG TTCTTTTGAG


TCCTTGTATG AATAAAAGGC TGGAAACCTA AA


Protein sequence 17 (SEQ ID NO:400)


2S Gene name: glypican 1


Unigene number: Ha.2699


Protein Acceeaion #: NP_002072


Signal sequence: none found


Pfam domain: Glypican protein (2-490]


30 Transmembrane domains: none found


Cellular Localization: plasma membrane


1 11 21 31 41 51


MELRARGWWL LCAAAALVAC ARGDPASKSR SCGEVRQIYG~AKGFSLSDVP60
QAEISGEHLR


y3 ICPQGYTCCT SEMEENLANR SHAELETALR DSSRVLQAML120
S ATQLRSEDDH FQHLLNDSER


TLQATFPGAF GELYTQNARA FRDLYSELRL YYRGANLHLE180
ETLAEFWARL LERLFKQLHP


QLLLPDDYLD CLGKQAEALR PFGEAPRELR LRATRAFVAA240
RSFVQGLGVA SDVVRKVAQV


PLGPECSRAV MKLVYCAHCL GVPGARPCPD YCRNVLKGCL300 - -
ANQADLDAEW RNLLDSMVLI


TDKFWGTSGV ESVIGSVHTW LAEAINALQD NRDTLTAKVI360
QGCGNPKVNP QGPGPEEKRR


4O RGKLAPRERP PSGTLEKLVS EAKAQLRDVQ DFWISLPGTL420
CSEIfMALSTA SDDRCWNGMA


RGRYLPEVMG DGLANQINNP EVEVDITKPD MTIRQQIMQL480
KIMTNRLRSA YNGNDVDPQD


ASDDGSGSGS


DNA sequence 1B (SEQ ID N0:401)


4S Gene name: NY-RSN-24 antigen


Unigene number: Ha.128425


Nucleic Acid Accession #: AP155102


Coding sequence: 27-908 -


1
1
1
1
l


SO I
,
I
I
I ~


GCGAGGGCGA GGGCGAGGCG GTGCTCATGG AGGAGGACCT60
GATCCAGCAG AGCCTGGACG


ACTACGACGC CGGCAGGTAC AGCCCGCGGC TGCTCACGGC120
GCACGAGCTG CCACTGGACG


CGCACGTGCT GGAACCGGAT GAGGACCTGC AGCGCCTGCA180
GCTCTCGCGC CAGCAGCTCC


AGGTCACGGG AGACGCCAGC GAGAGCGCCG AGGACATCTT240
CTTCCGGCGG GCCAAGGAGG


SS GCATGGGCCA GGACGAGGCG CAGTTCAGCG TGGAGATGCC300
ACTCACCGGC AAGGCCTACC


TGTGGGCCGA CAAGTACCGG CCACGCAAGC CGCGCTTCTT360
CAACCGCGTG CACACGGGCT


TCGAGTGGAA CAAGTACAAC CAGACGCACT ACGACTTTGA420
CAACCCACCG CCCAAGATCG


TGCAGGGATA CAAGTTCAAC ATCTTCTACC CCGACCTCAT480
CGACAAGCGC TCCACGCCCG


AGTACTTCCT GGAGGCCTGC GCCGACAACA AGGATTTCGC540
CATCCTGCGC TTCACGCGGG


GCCGCCTACG AGGACATCGC TTTCAAGATC GTCAACCGCG600
AGTGGGAATA CTCGCACCGC


CACGGCTTCC GCTGCCAGTT TGCCAACGGC ATCTTCCAGC660
TGTGCTTTCA CTTCAAGCGC


TACCGCTATC GGCGGTGACG GCCCTGGGGA ACGGCAGGCC720
AGGAGGGCCG AGGGCCACAC


GGGTGCCACA GCCCAGGTCG GAGTGGCCCA GCCGGCAGGC780
TTGTTCTTCA GCATCCGACG


GGAACATCTC CAACAGAAGC AAAACGGAAA GTGCCTCCCG840
GACCCCCAGA GGGCCACCCA


6S ACCTCACCAG TCACCAGCCC CAGACCACCC ACAGCCCCTC900
CCAGACACCC CGCCTCATCT


AGTT CCGTTTGTTT CTCTAAAAAG ACTTGTAGGT GGGAAAAAAA960
ATCTTTTGTT
GGAAAT


_ 1020
CTCATGGAAT TGGCCTATTG GCAAGATCGC ATGTTTTTTT
AATAAACGTT GTATTTTAGA


ATAAAA


O Protein sequence 18 (SEQ ID N0:402)


Gene name: NY-REN-24 antigen


Unigene number: Hs.128425


Protein Accession #: AAD4286B


Signal sequence: none found


7S Transmembrane domains: none found


Cellular Localization: plasma membrane


1 11 21 31 41 51


GEGEAVLME EDLIQQSLDD YDAGRYSPRL LTAHELPLDA60
HVLEPDEDLQ RLQLSRQQLQ


gO TGDASESAE DIFFRRAItEG MGQDEAQFSV EMPLTGKAYL120
WADKYRPRKP RFFNRVHTGF


WNKYNQTHY DFDNPPPKIV QGYKFNIFYP DLIDKRSTPE180
YFLEACAI7NK DFAILRFTRG


LRGHRFQDR QPRVGILAPP RLPLPVCQRH LPAVLSLQAL240
PLSAVTALGN GRPGGPRATR


PQPRSEWPS RQACSSASDG NISNRSKTES ASRTPRGPPN300
LTSHQPQTTH SPSQTPRLIW


153


CA 02459219 2004-03-17
;f ;:w .(....: ...~.. . ' ;~..t~ ~.'.'~4 n YY i ~;~ ; ;:ws~ :1: ~~k :! r ; _t;
", 'F~rv -9 F ' r 1. ~ t $
l i w ~d~
DNA sequence Z9 iSEQ ID N0:403)


Gene name: tumor necrosis factor receptor
auperfamily, member 1A


Unigene number: Hs.159


Probeset Accession #: BE295782
S


Nucleic Acid Accession #: NM_001065


Coding sequence: 256-1623 .


1 1l 21 31 41 51


CGGCCCAGTG ATCTTGAACC CCAAAGGCCA GAACTGGAGC60
CTCAGTCCAG AGAATTCTGA


I GAAAATTAAA GCAGAGAGGA GGGGAGAGAT CACTGGGACC120
O AGGCCGTGAT CTCTATGCCC


GAGTCTCAAC CCTCAACTGT CACCCCAAGG CACTTGGGAC180
GTCCTGGACA GACCGAGTCC


CGGGAAGCCC CAGCACTGCC GCTGCCACAC TGCCCTGAGC240
CCAAATGGGG GAGTGAGAGG


CCATAGCTGT CTGGC_ATGGG CCTCTCCACC GTGCCTGACC300
TGCTGCTGCC GCTGGTGCTC


CTGGAGCTGT TGGTGGGAAT ATACCCCTCA GGGGTTATTG360
GACTGGTCCC TCACCTAGGG


1 GACAGGGAGA AGAGAGATAG TGTGTGTCCC CAAGGAAAAT420
S ATATCCACCC TCAAAATAAT


TCGATTTGCT GTACCAAGTG CCACAAAGGA ACCTACTTGT480
ACAATGACTG TCCAGGCCCG


GGGCAGGATA CGGACTGCAG GGAGTGTGAG AGCGGCTCCT540
TCACCGCfTC AGAAAACCAC


CTCAGACACT GCCTCAGCTG CTCCAAATGC CGAAAGGAAA600
TGGGTCAGGT GGAGATCTCT


TCTTGCACAG TGGACCGGGA CACCGTGTGT GGCTGCAGGA660
AGAACCAGTA CCGGCATTAT


ZO TGGAGTGAAA ACCTTTTCCA GTGCTTCAAT TGCAGCCfCT720
GCCTCAATGG GACCGTGCAC


CTCTCCTGCC AGGAGAAACA GAACACCGTG TGCACCTGCC7B0
ATGCAGGTTT CTTTCTAAGA


GAAAACGAGT GTGTCTCCTG TAGTAACTGT AAGRAAAGCC840
TGGAGTGCAC GAAGTTGTGC


CTACCCCAGA TTGAGAATGT TAAGGGCACT GAGGACTCAG900
GCACCACAGT GCTGTTGCCC


CTGGTCATTT TCFTTGGTCT TTGCCTTTTA TCCCTCCTCT960
TCATTGGTTT AATGTATCGC


.~ TACCAACGGT GGAAGTCCAA GCTCTACTCC ATTGTTTGTG1020
LS GGAAATCGAC ACCTGAAAAA


GAGGGGGAGC TTGAAGGAAC TACTACTAAG CCCCTGGCCC1080
CAAACCCAAG CTTCAGTCCC


ACTCCAGGCT TCACCCCCAC CCTGGGCTTC AGTCCCGTGC1140
CCAGTTCCAC CTTCACCTCC


AGCTCCACCT ATACCCCCGG TGACTGTCCC AACTTTGCGG1200
CTCCCCGCAG AGAGGTGGCA


CCACCCTATC AGGGGGCTGA CCCCATCCTT GCGACAGCCC1260
TCGCCTCCGA CCCCATCCCC


3O AACCCCC~TC AGAAGTGGGA GGACAGCGCC CACAAGCCAC1320
AGAGCCTAGA CACTGATGAC


CCCGCGACGC TGTACGCCGT GGTGGAGAAC GTGCCCCCGT1380
TGCGCTGGAA GGAATTCGTG


CGGCGCCTAG GGCTGAGCGA CCACGAGATC GATCGGCTGG1440
AGCTGCAGAA CGGGCGCTGC


CTGCGCGAGG CGCAATACAG CATGCTGGCG ACCTGGAGGC1500
GGCGCACGCC GCGGCGCGAG


GCCACGCTGG AGCTGCTGGG ACGCGTGCTC CGCGACATGG1560
ACCTGCTGGG CTGCCTGGAG


3 GACATCGAGG AGGCGCTTTG CGGCCCCGCC GCCCTCCCGC1620
S CCGCGCCCAG TCTTCTCAGA


TGAGGCTGCG CCCCTGCGGG CAGCTCTAAG GACCGTCCTG1680
CGAGATCGCC TTCCAACCCC


_ 1740
ACTTTTTTCT GGAAAGGAGG GGTCCTGCAG GGGCAAGCAG
GAGCTAGCAG CCGCCTACTT


GGTGCTAACC CCTCGATGTA CATAGCTTTT CTCAGGTGCC1800
TGCGCGCCGC CGACAGTCAG


CGCTGTGCGC GCGGAGAGAG GTGCGCCGTG GGCTCAAGAG1860
CCTGAGTGGG TGGTTTGCGA


4O GGATGAGGGA CGCTATGCCT CATGCCCGTT TTGGGTGTCC1920
TCACCAGCAA GGCTGCTCGG


GGGCCCCTGG TTCGTCCCTG AGCCTTTTTC ACAGTGCATA1980
AGCAGTTTTT TTTGTTTTTG


TTTTGTTTTG TTTTGTTTTT AAATCAATCA TGTTACACrA2040
ATAGAAACTT GGCACTCCTG


TGCCCTCTGC CTGGACAAGC ACATAGCAAG CTGAACTGTC2100
CTAAGGCAGG GGCGAGCACG


AACAATGGG GCCTTCAGCT GGAGCTGTGG ACTTTTGTAC2160
ATACACTAAA ATTCTGAAGT


4S T


Protein sequence 19 (SEQ ID N0:404)


Gene name: tumor necrosis factor member
receptor superfamily, 1A


Unigene number: Ha.159


SO Protein Accession #: NP 001056


Signal sequence: 1-29


TNFR domain: 44-81, 84-125, 127-166,
168-195


Tranamembrane domains: 211-234


Cellular Localization: plasma membrane


S 1 11 21 31 91 51
S


MGLSTVPDLL LPLVLLELLV GIYPSGVIGL HPQNNSICCT
VPHLGDREKR DSVCPQGKYI 60


KCHKGTYLYN DCPGPGQDTD CRECESGSFT QVEISSCTVD
ASENHLRHCL SCSKCRKEMG 120


RDTVCGCRKN QYRHYWSENL FQCFNCSLCL GFFLRENECV
NGTVHLSCQE KQNTVCTCHA 1B0


60 SCSNCKKSLE CTKLCLPQIE NVKGTEDSGT GLMYRYQRWK
TVLLPLVIFF GLCLLSLLFI 240


SKLYSIVCGK STPEKEGELE GTTTKPLAPN STFTSSSTYT
PSFSPTPGFT PTLGFSPVPS 300


PGDCPNFAAP RREVAPPYQG ADPILATALA LDTDDPATLY
SDPIPNPLQK WEDSAHKPQS 360


AVVENVPPLR WKEFVRRLGL SDHEIDRLEL TPRREATLEL
QNGRCLREAQ YSMLATWRRR 420


LGRVLRDMDL LGCLEDIEEA LCGPAALPPA
PSLLR


SS


DNA sequence 20 (SEQ ID N0:405)


Gene name: prominin (mouse)-like
1


Unigene number: Ha.112360


Probeset Accession #: 840057


.~ Nucleic Acid Accession #: NM 006017
/O


Coding sequence: 38-2635


1 11 21 31 41 51


CCAAGTTCTA CCTCATGTTT GGAGGATCTT TCGGCTCCCT
GCTAGCTATG GCCCTCGTAC 60


7S GTTGCTGCTG GGGCTGTGCG GGAACTCCTT CCACAGATGC
TTCAGGAGGG CAGCCTTCAT 120


TCCTAAGGCT TGGAATTATG AATTGCCTGC ACTCCCATAA
AACAAATTAT GAGACCCAAG 1B0


AGCTGGACCC ATTGGCATTC TCTTTGAACT TGGTACAGCC
AGTGCATATC TTTCTGTATG 240


GCGTGATTTC CCAGAAGATA CTTTGAGAAA AATCCAAAAT
ATTCTTACAG AAGGCATATG 300


TGATTATGAC AAGCCAGAAA CTGTAATCTT ATGAAGCAGG
AGGTCTAAAG ATTGTCTACT 360


S GATTATTCTA TGCTGTGTCC TGGGGCTGCT TGGTGGGGTA
O GTTTATTATT CTGATGCCTC .420


TTTCTTTTGT ATGTGTCGTT GCTGTAACAA AGCGACAGAA
ATGTGGTGGA GAAATGCACC 480


GGAAAATGGG CCCTTCCTGA GGAAATGCTT TTTGTATAAT
TGCAATCTCC CTGTTGGTGA 540


AATAAGCATT GGCATCTTCT ATGGTTTTGT CCCGGATCAA
GGCAAATCAC CAGGTAAGAA 600


AAGGAGTCGG AAACTGGCAG ATAGCAATTT TGAATGAAAC
CAAGGACTTG CGAACTCTCT 660


154
._ .,


CA 02459219 2004-03-17
.,~ ~w. ' , " i:; .i~ ~'xi ;~ _. :' ~' . '~ s:~ ' ~:~.~:Iw~"'s: '. j~ F ~t (
';t . .".,z , »,~ '~
,.
TCCAGAGCAA ATCAAATATA TATTGGCCCA GTACAACACT720
ACCAAGGACA AGGCGTTCAC


RGATCTGAAC AGTATCAATT CAGTGCTAGG AGGCGGAATT780
CTTGACCGAC TGAGACCCAA


CATCATCCCT GTTCTTGATG AGATTAAGTC CATGGCAACA840
GCGATCAAGG AGACCAAAGA


GGCGTTGGAG AACATGAACA GCACCTTGAA GAGCTTGCAC900
CAACAAAGTA CACAGCTTAG


S CAGCAGTCTG ACCAGCGTGA ARACTAGCCT GCGGTCATCT960
CTCAATGACC CTCTGTGCTT


GGTGCATCCA TCAAGTGAAA CCTGCAACAG CATCAGATTG1020
TCTCTAAGCC AGCTGAATAG


CAACCCTGAA CTGAGGCAGC TTCCACCCGT GGATGCAGAA1080
CTTGACAACG TTAATAACGT


TCTTAGGACA GATTTGGATG GCCTGGTCCA ACAGGGCTAT1140
CAATCCCTTA ATGATATACC


TGACAGAGTA CAACGCCAAA CCACGACTGT CGTAGCAGGT1200
ATCAAAAGGG TCTTGAATTC


1 CATTGGTTCA GATATCGACA ATGTAACTCA GCGTCTTCCT1260
O ATTCAGGATA TACTCTCAGC


ATTCTCTGTT TATGTTAATA ACACTGAAAG TTACATCCAC1320
AGAAATTTAC CTACATTGGA


AGAGTATGAT TCATACTGGT GGCTGGGTGG CCTGGTCATC1380
TGCTCTCTGC TGACCCTCAT


CGTGATTTTT TACTACCTGG GCTTACTGTG TGGCGTGTGC1440
GGCTATGACA GGCATGCCAC


CCCGACCACC CGAGGCTGTG TCTCCAACAC CGGAGGCGTC1500
TTCCTCATGG TTGGAGTTGG


I ATTAAGTTTC CTCTTTTGCT GGATATTGAT GATCATTGTG1560
S GTTCTTACCT TTGTCTTTGG


TGCAAATGTG GAAAAACTGA TCTGTGAACC TTACACGAGC1620
AAGGAATTAT TCCGGGTTTT


GGATACACCC TACTTACTAA ATGAAGACTG GGAATACTAT1680
CTCTCTGGGA AGCTATTTAA


TARATCAAAA ATGAAGCTCA CTTTTGAACA AGTTTACAGT1740
GACTGCAAAA AAAATAGAGG


CACTTACGGC ACTCTTCACC TGCAGAACAG CTTCAATATC1800
AGTGAACATC TCAACATTAA


ZO TGAGCATACT GGAAGCATAA GCAGTGAATT GGAAAGTCfG1860
AAGGTAAATC TTAATATCTT


TCTGTTGGGT GCAGCAGGAA GAAAAAACCT TCAGGATTTT1920
GCTGCTTGTG GAATAGACAG


AATGAATTAT GACAGCTACT TGGCTCAGAC TGGTAAATCC1980
CCCGCAGGAG TGAATCTTTT


ATCATTTGCA TATGATCTAG AAGCAAAAGC AAACAGTTTG2040
CCCCCAGGAA ATTTGAGGAA


CTCCCTGAAA AGAGATGCAC RAACTATTAA AACAATTCAC2100
CAGCAACGAG TCCTTCCTAT


ZS AGAACAATCA CTGAGCACTC TATACCAAAG CGTCAAGATA2160
CTTCAACGCA CAGGGAATGG


ATTGTTGGAG AGAGTAACTA GGATTCTAGC TTCTCTGGAT2220
TTTGCTCAGA ACTTCATCAC


AAACAATACT TCCTCTGTTA TTATTGAGGA AACTAAGAAG2280
TATGGGAGAA CAATAATAGG


ATATTTTGAA CATTATCTGC AGTGGATCGA GTTCTCTATC2390
AGTGAGAAAG TGGCATCGTG


CAAACCTGTG GCCACCGCTC TAGATACTGC TGTTGATGTC2400
TTTGTGTGTA GCTACATTAT


3 CGACCCCTTG AATTTGTTTT GGTTTGGCAT AGGAAAAGCT2460
O ACTGTATTTT TACTTCCGGC


TCTAATTTTT GCGGTAAAAC TGGCTAAGTA CTATCyTCGA2520
ATGGATTCGG AGGACGTGTA


CGATGATGTT GAAACTATAC CCATGAAAAA TATGGAAAAT2580
GGTAATAATG GTTATCATAA


AGATCATGTA TATGGTATTC ACAATCCTGT TATGACAAGC2640
CCATCACAAC ATTGATAGCT


GATGTTGAAA CTGCTTGAGC ATCAGGATAC TCAAAGTGGA2700
~ AAGGATCACA GATTTTTGGT


3S AGTTTCTGGG TCTACAAGGA CTTTCCAAAT CCAGGAGCAA2760
CGCCAGTGGC AACGTAGTGA


CTCAGGCGGG CACCAAGGCA ACGGCACCAT TGGTCTCTGG2820
GTAGTGCTTT AAGAATGAAC


ACAATCACGT TATAGTCCAT GGTCCATCAC TATTCAAGGA2880
TGACTCCCTC CCTTCCfGTC


TATTTTTGTT TTTTACTTTT TTACACTGAG TTTCTATTTA2940
GACACTACAA CATATGGGGT


GTTTGTTCCC ATTGGATGCA TTTCTATCAA AACTCTATCA3000
AATGTGATGG CTAGATTCTA


p ACATATTGCC ATGTGTGGAG TGTGCT,GAAC ACACACCAGT3060
TTACAGGAAA GATGCATTTT


GTGTACAGTA AACGGTGTAT ATACCTTTTG TTACCACAGA3120
GTTTTTTAAA CAAATGAGTA


TTATAGGACT TTCTTCTAAA TGAGCTAAAT AAGTCACCAT3180
TGACTTCfTG GTGCTGTTGA


AAATAATCCA TTTTCACTAA AAGTGTGTGA AACCTACAGC3240
ATATTCTTCA CGCAGAGATT


TTCATCTATT ATACTTTATC AAAGATTGGC CATGTTCCAC3300
TTGGAAATGG CATGCAAAAG


p CCATCATAGA GAAACGTGCG TAACTCCATC TGACAAATTC3360
'tSAAAAGAGAGA GAGAGATCTT


GAGAGAGAAA TGCTGTTCGT TCAAAAGTGG AGTTGTTTTA3420
ACAGATGCCA ATTACGGTGT


ACAGTTTAAC AGAGTTTTCT GTTGCATTAG GATAAACATT3480
AATTGGAGTG CAGCTAACAT


GAGTATCATC AGACTAGTAT CAAGTGTTCT AAAATGAAAT3540
ATGAGAAGAT CCTGTCACAA


TTCTTAGATC TGGTGTCCAG CATGGATGAA ACCTTTGAGT3600
TTGGTCCCTA AATTTGCATG


S AAAGCACAAG GTAAATATTC ATTTGCTTCA GGAGTTTCAT3660
O GTTGGATCTG TCATTATCAA


AAGTGATCAG CAATGAAGAA CTGGTCGGAC AAAATTTAAC3720
GTTGATGTAA TGGAATTCCA


GATGTAGGCA TTCCCCCCAG GTCTTTTCAT GTGCAGATTG3780
CAGTTCTGAT TCATTTGAAT


AAAAAGGAAC TTGGC


S Protein sequence 20 (SEQ ID N0:406)
S


Gene name: prominin (mouse)-like 1


Unigene number: Hs.112360


Protein Accession #: NP 006008


Signal sequence: 1-21
'


n Transmembrane domains: 105-127, 157-179, 6
6V 438-460, 482-504, 784-80


Cellular Localization: plasma membrane


1 11 21 31 41 51


MALVLGSLLL LGLCGNSFSG GQPSSTDAPK AWNYELPATN60
YETQDSHKAG PIGILFELVH


6S IFLYWQPRD FPEDTLRKFL QKAYESKIDY DKPETVILGL120
KIVYYEAGII LCCVLGLLFI


ILMPLVGYFF CMCRCCNKCG GEMHQRQKEN GPFLRKCFAI180
SLLVICIIIS IGIFYGPVAN


HQVRTRIKRS RKLADSNFKD LRTLLNETPE QIKYILAQYN240
TTKDKAFTDL NSINSVLGGG


ILDRLRPNII PVLDEIKSMA TAIKETKEAL ENMNSTLKSL300
HQQSTQLSSS LTSVKTSLRS


SLNDPLCLVH PSSETCNSIR LSLSQLNSNP ELRQLPPVDA360
ELDDTVNNVLR TDLDGLVQQG


7O YQSLNDIPDR VQRQTTTWA GIKRVLNSIG SDIDNVTQRL420
PIQDILSAFS VYVNNTESYI


HRNLPTLEEY DSYWWLGGLV ICSLLTLIVI FYYLGLLCGV480
CGYDRHATPT TRGCV$NTGG


VFLMVGVGL9 FLFCWILMII VVLTFVFGAN VEKLICEPYT540
SKELFRVLDT PYLLNEDWEY


YLSGKLFNKS KMKLTFEQVY SDCKKNRGTY GTLHLQNSFN600
ISEHLNINEH TGSISSELES


LKVNLNIFLL GAAGRKNLQD FAACGIDRMN YDSYLAQTGK660
SPAGVNLLSF AYDLEAKANS


IS LPPGNLRNSL XRDAQTIKTI HQQRVLPIEQ SLSTLYQSVK720
ILQRTGNGLL ERVTRILASL


DFAQNFITNN TSSVIIEETK KYGRTIIGYF EHYLQWIEFS780
ISEKVASCKP VATALDTAVD


VFLCSYIIDP LNLFWFGIGK ATVFLLPALI FAVKLAKYYR840
RMDSEDVYDD VETIPMKNME


NGNNGYHKDH VYGIHNPVMT SPSQH


DNA sequence 21 (SEQ ID N0:907) '~"' '' ,,


Gene name: G protein-coupled receptor 39 '' .


Unigene number: Hs.85339


Nucleic Acid Accession #: NM,-,001508


Coding sequence: 1-1362


. . ,'.'": . .~ ' , , ,
1S5


CA 02459219 2004-03-17
, ..., r ,~ t "' y ". ~. y r ~~
;~:.:~ ~~~f.-..~" J,,. ~j~ ~;'s t~,.iT p::.~ ''~ d' ~.~:.~~~.!..; f''s' ~t('
~' ,t .i~' ~ .,.~ $ .s
..~ . ~~ ~~ ~ v~o~:~~~~~
1 11 21 31 41 S1 '


TGGCTTCAC CCAGCCTCCC GGGCAGTGAC TGCTCCCAAA60
TCATTGATCA CAGTCATGTC
A


_ 120
CCCGAGTTTG AGGTGGCCAC CTGGATCAAA ATCACCCTTA
TTCTGGTGTA CCTGATCATC


S TTCGTGATGG GCCTTCTGGG GAACAGCGCC ACCATTCGGG180
TCACCCAGGT GCTGCAGAAG


AAAGGATACT TGCAGAAGGA GGTGACAGAC CACATGGTGA240
GT2TGGCTTG CTCGGACATC


TTGGTGTTCC TCATCGGCAT GCCCATGGAG TTCTACAGCA300
TCATCTGGAA TCCCCTGACC


ACGTCCAGCT ACACCCTGTC CTGCAAGCTG CACACTTTCC360
TCTTCGAGGC CTGCAGCTAC


GCTACGCTGC TGCACGTGCT GACACTCAGC TTTGAGCGCT420
ACATCGCCAT GTGTCACCCC


1 TTCAGGTACA AGGCfGTGTC GGGACCTTGC CAGGTGAAGC480
O TGCTGATTGG CTTCGTCZ'GG


GTCACCTCCG CCCTGGTGGC ACTGCCCTTG CTGTTTGCCA540
TGGGTACTGA GTACCCCCTG


GTGAACGTGC CCAGCCACCG GGGTCTCACT TGCAACCGCT600
CCAGCACCCG CCACCACGAG


CAGCCCGAGA CCTCCAATAT GTCCATCTGT ACCAACCTCT660
CCAGCCGCTG GACCGTGTTC


CAGTCCAGCA TCTTCGGCGC CTTCGTGGTC TACCTCGTGG720
TCCTGCTCTC CGTAGCCTTC


S ATGTGCTGGA ACATGATGCA GGTGCTCATG AAAAGCCAGA780
AGGGCTCGCT GGCCGGGGGC


ACGCGGCCTC CGCAGCTGAG GAAGTCCGAG AGCGAAGAGA840
GCAGGACCGC CAGGAGGCAG


ACCATCATCT TCCTGAGGCT GATTGTTGTG ACATTGGCCG900
TATGCTGGAT GCCCAACCAG


ATTCGGAGGA TCATGGCTGC GGCCAAACCC AAGCACGACT960
GGACGAGGTC CTACTTCCGG


GCGTACATGA TCCTCCTCCC CTTCTCGGAG ACGTTTTTCT1020
ACCTCAGCTC GGTCATCAAC


2O CCGCTCCTGT ACACGGTGTC CTCGCAGCAG TTTCGGCGGG1080
TGTTCGTGCA GGTGCTGTGC


TGCCGCCTGT CGCTGCAGCA CGCCAACCAC GAGAAGCGCC1140
TGCGCGTACA TGCGCACTCC


ACCACCGACA GCGCCCGCTT TGTGCAGCGC CCGTTGCTCT1200
TCGCGTCCCG GCGCCAGTCC


TCTGCAAGGA GAACTGAGAA GATTTTCTTA AGCACTTTTC1260
AGAGCGAGGC CGAGCCCCAG


TCTAAGTCCC AGTCATTGAG TCTCGAGTCA CTAGAGCCCA1320
ACTCAGGCGC GAAACCAGCC


S AATTCTGCTG CAGAGAATGG TTTTCAGGAG CATGAAGTTT
GA
2


Protein sequence 21 [SEQ ID N0:408)


Gene name: G protein-coupled receptor 39


Unigene number: Hs.85339


3 Protein Accession #: NM_001508, NP 001409
O


Signal sequence: none found


Pfam domains: 7tm 1 [72-172, 224-344]


Transmembrane domains: 32-54, 68-90, 111-133,
i81-173, 221-243, 280-301, 320-342


Cellular Localization: plasma membrane


3S 1 11 21 31 41 Sl


MASPSLPGSD CSQIIDHSHV PEFEVATWIK ITLILVYLII60
FVMGLLGNSA TIRVTQVLQK


KGYLQKEVTD HMVSLACSDI LVFLIGMPME FYSIIWNPLT120
TSSYTLSCKL HTFLFEACSY


ATLLHVLTLS FERYIAICHP FRYKAVSGPC QVKLLIGFVW180 ,
VTSALVALPL LPAMGTEYPL


,~ VNVPSHRGLT CNRSSTRHHE QPETSNMSIC TNLSSRWTVF240
QSSIFGAFW YLVVLLSVAF


MCWNMMQVLM KSQKGSLAGG TRPPQLRKSE SEESRTARRQ300
TIIFLRLIVV TLAVCWMPNQ


IRRIMAAAKP K<mWTR.SYFR AYMILLPFSE TPFYLSSVIN360
PLLYTVSSQQ FRRVPVQVLC


CRLSLQHANH EICRLRVHAHS TTDSARFVQR PLLFASRRQS420
SARRTEKIFL STFQSEAEPQ


SICSQSLSLES LEPNSGAKPA NSAAENGFQE HEV


4S


TABLE BA ABOUT 1260 GENES UP-REGULATED IN GLIOBLASTOMA COMPARED TO NORMAL
ADULT TISSUES
Table 8A lists about 126D genes up-regulated in gfioblastoma compared to
normal adult 8ssues. These were selected from 59680 prottesets on the
AffymeUixIEos Hu03 GeneChtp
array such that the raLo of'average' glioblastoma to'average' normal adult
tissues was greater than or equal lo 2.5. The 'average" gho6tastoma level was
set to the 75th peroenhle
S O amongst various glioblastoma tumors. The'average' normal adult tissue
level was set to the 851h peroen8le amongst i(ano~s non-malignant tissues. 1n
order to remove gene
specfic background levels of non-speGfic hybridizafion, the IDOi percentile
value amongst the non-malignant tissues was subtracted from both the numerator
and the denominator
before the rafio was evaluated.
Pkey Unique Eos probeset identifier number
ExAccn: Fxemplar Accession number, Genbank accession number , . ~ , w
S S UnigenelD: Umgene number
Umgene TiBe: Unigene gene U8e
R1: Rafio of 75th peroenbte tumor to 85th percenfile normal body tissue
Pkey E.xAccnUnigenelDUnigene TtBe Ri


60 431917D16181Hs.2868peripheral myelin proteinT5.2
2


427343AI880044Hs protein kinase C binding74
176977protein 2 6


455601AI368680Hs SRY (sex determining 74,2
816 region Yrbox 2


428321AI699994Hs.2868penpheral myelin protein716
2


412719. Hs.129911ESTs 70.7
AW016610


6S 449494AW237014Hs.315369Homo Sapiens cDNA: FLJ2307566.3
fis, clone L


415817U88967Hs.70867protein tyrosine phosphatase,643
receptor t


413472BE242870Ns.75379solute cartier family 60.1
1 (filial high affi


456759BE259150Hs.127792delta (Drasophila)hke 52.3
3


435147AL133731Hs Homo Sapiens mRNA; cDNA46
4774 DKFZp761 C1712 (f 7


7O 425842AI587490Hs NK-2 (Drosophila) homolog401
159623B


412733AA984472Hs.74554KIAAODBD protein 39.0


418375NNL003081Hs,B4389synaptosomal-associated38.7
protein, 25kD


453392U23752Hs.32964SRY (sex detertnming 37.2
region Y)-box 11


423849AL157425Hs.133315Homo Sapiens mRtJA, 36.8
cDtVA DKFZp761J1324
(f


7S 413333M74028Hs fibro6last growth factor32
75297 1 {acidic) 8


416829A8013805Hs.80220catenm {cadherinassocialed31.8
protein), d


431941AK000106Hs Hamo Sapiens cDNA FLJ20099318
272227fis, clone CO


436878BE465204Hs.47448ESTs 31.4


426325D28114Hs.169309myelin-associated ollgodendrocyle30.9
basic


O 425057AA826434Hs.1619achaete~scute complex ~.4
(Drosaphila) homol


446711AFi69692Hs,1245Dprotocadherin 9 30.2


439415F05538Hs,12825ESTs 28.3


430838N46664Hs hypothe8cal protein
169395FWt2015


186


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WO 03/025138 PCT/US02/29560
429466M85835Hs.12827ESTs 25.9


447004AW296968Hs.157539ESTs 25.3


424581M62062Hs.150917catenin (cadherin-associated24.8
protein), a


452744AI267652Hs.30504Homo Sapiens mRNA; 24.8
cDNA DKFZp434E082
(fr


441285NM-002374Hs.167microtubuie-associated24.3
protein 2


453642AI370936Hs.34074dipep6dylpeptidase 24.3
VI


424140248051Hs.141308myelin oligodendrocyte24.2
glycoprotein


450133AW969769Hs.105201ESTs 24.2


408562A1436323Hs.31141Homo Sapiens mRNA for 23.3
KIAA1568 protein,


1 448672A1955511Hs.225106ESTs 22.7
0


435708A1362949Hs.75169ESTs 22.0


407034U84540 gb:Human dystrobrevin 21.9
isoform DTN-3 (DTN


407168845175Hs.117183ESTs 21.7


431019NM Hs.2714forkhead box G1B 21.5
005249


1 409049_ Hs.146343ESTs 21.4
AI423132


433896AW294729Hs.274461ESTs 21.1


445041T64183Hs.282982solute carver 21.0


418738AW388633Hs.6682solute carrier family 20.4
7, (cationic amino


444378841339Hs.12569ESTs 20
0


20411305BE241596Hs.69547myelin basic protein .
19.g


437414AW894071Hs.48448hypothetical protein 19.8
DKFZp547C176


441016AW138653Hs.25845ESTs 19.6


440435AL042201Hs.21273transcription factor 18.5
NYDsplO


438209AL120659Hs.6111aryl-hydrocarbon receptor18.4
nuclear iransl


25452461N78223Hs.108106transcriptionfactor 18.1


409395U46745Hs.54435dystrobrevin, alpha 18.1


417183852089Hs.172717ESTs 18.0


409638AW450420Hs.21335ESTs 18.0


-028392H10233Hs.2265secretory granule,neuroendocrine18.0
protei


449611A1970394Hs.197075ESTs 17.0


446692244514Hs.156829Homo Sapiens mRNA for 16.9
KIAA1763 protein,


425088AA663372Hs.169395hypothetical protein 16.9
FLJ12015


444471AB020684Hs.11217KIAA0877 protein 16.8


421659NM_014459Hs.106511protocadherin 17 16.7


35431725X65724Hs.2839Nome disease (pseudoglioma)16.6


429276AF056085Hs.198612G protein-coupled receptor16.6
51


416892L24498Hs.80409growth arrest and DNA-damage-inducibte,16.5


-041440AI807981Hs.30495ESTs 15.7


449433AI672096Hs.9012ESTs, Weakly similar 15.7
to 526650 DNA-bindi


421264AL039123Hs.103042microtubule-associated15.5
protein 1 B


415910U20350Hs.78913chemokine (GX3-C) receptor15.3
1


413597AW302885Hs.117183ESTs 15.1


424945A1221919Hs.173438hypothetical protein 14.9
FLJ10582


447414D82343Hs.18551neuroblastoma (nerve 14.9
tissue) protein


45426269H15302Hs.168950Homo Sapiens mRNA; 14.8
cDNA DKFZp566A1046
(f


416857AA188775Hs.292453ESTs 14.7


419721NM Hs.288650aquaporin 4 14.6
001650


411078A1222020Hs.182364CocoaCrisp 14.4


453924849295Hs.24886ESTs 14
4


409389AB007979Hs.301281Homo Sapiens mRNA, .
chromosome 1 specific 14.3


430130AL137311Hs.234074Homo Sapiens mRNA; 14.1
cDNA DKFZp761G02121
(


410909AW898161Hs.53112ESTs, Moderately similar14.0
to ALUB_HUMAN A


412266N59006Hs.26133ESTs 14.0


412986X81120Hs.75110cannabinoid receptor 14.0
1 (brain)


55424790AL119344Hs.13326ESTs, Weakly similar 14.0
to 2004399A chromos


439239A1031540Hs.235331ESTs 14.0


441497851064Hs.23172ESTs 14.0


445495BE622641Hs.38489ESTs, Weakly similar 14.0
to 138022 hypotheti


41,4245BE148072Hs.75850WAS protein family, 13.7
member 1


60429900AA460421Hs.30875ESTs 13.6


448595AB014544Hs.21572KIAA0644 gene product 13.6


449605AW138581Hs.198416ESTs 13.6


452526W38537Hs.280740hypothetical protein 13.6
MGC3040


420547AF155140Hs.98738gonadotropin-regulated13.3
testicular RNA he


65441350AB020690Hs.7782paraneoplastic antigen13.3
MA2


420077AW512260Hs.87767ESTs 13.2


424120T80579Hs.290270ESTs 13.2


456965AW13i888Hs.172792ESTs, Weakly similar 13.2
to hypothetical pro


423361AW170055Hs.47628ESTs 13
1


428409AW117207Hs.98523ESTs .
12.9


417160N76497Hs.1787proteolipid protein 12.6
1 (Pelizaeus-Meabac


451621AI879148Hs.26770fatty acid binding 12.5
protein 7, brain


411379AI816344Hs.12554ESTs, Weakly similar 12.5
to NPL4_HUMAN NUCLE


436954AA740151Hs.130425ESTs 12
4


75430691C14187Hs.103538ESTs .
12.4


433551A1985544Hs.12450protocadherin 9 12,4


422544AB018259Hs.1181d0KIAA0716 gene product 12.2


427540812014Hs.20976ESTs , 12.1


435624AF218942Hs.24889formin 2 12
1


g 415849820529Hs.6806ESTs ,
0 12,1


428845AL157579Hs.153610KIAA0751 gene product il.g


442671A1005668Hs.134779EST 11.9


444396T65213Hs.4257ESTs 11.8


157


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WO 03/025138 PCT/US02/29560
452752AW044058Hs.33578KIAA0820 protein 11.8


425523AB007948Hs.158244KIAA0479 protein 11.8


416072AL110370Hs.79000growth associated protein11.7
43


440184AB002297Hs.7022dedicator of cyto-kinesis11
3 7


428976AL037824Hs.194695ras homolog gene family,.
member I 11.6


444783AK001468Hs.62180aniflin (Drosophila 11.6
Scraps homology, act


448299AA497044Hs.20887hypothetical protein 11.6
FLJ10392


414214D49958Hs.75819glycoprotein M6A 11.5


428982NM-005097Hs.194704leucine-rich, glicma 11.5
inactivated 1


l0405238 11,4


420362079734Hs.97206huntingiin interacting11.4
protein 1


422980N46569Hs.76722CCAAT/enhancer binding11.4
protein (CIEBP),


424918813982Hs.169309myelin-associated oligodendrocyte11.4
basic


434277X77748Hs.3786glutamate receptor, 11.4
metabotropic 3


15451952AL120173Hs.301663ESTs 11.3


408829Ntvt_006042Hs.48384heparan sulfate (glucosamine)11.3
3-0-sulfot


424278AK000723Hs.144517hypothetical protein 11.3
FLJ20716


429418AI381028Hs.118769ESTs 11.3


429918AW873986Hs.119383ESTs 11
3


443912837257Hs.184780ESTs .
11.3


448743AB032962Hs.21896KIAA1136 protein 11.3


420092AA814043Hs.88045ESTs 11.2


408081AW451597Hs.167409ESTs 11,2


411642NM Hs.71132neuroligin 1 10.9
014932


415170844386Hs.164578ESTs 10.9


426320W47595Hs.169300transforming growth 10.8
factor, beta 2


450568AL050078Hs.25159Homo Sapiens cDNA FLJ1078410.8
fis, clone NT


425799T08133Hs.182906Homo Sapiens mRNA for 10.8
KIAA1872 protein,


423853AB011537Hs.133466slit (Drosophila) homolog1D.7
1


30400293N51002Hs.306480Homo Sapiens mRNA; 10.7
cDNA DKFZp761E2112
(f


447773AI423930Hs.36790ESTs, Weakly similar 10.7
to putative p150 (H


448321NM Hs.20912adenomatous polyposis 10.5
005883 coli like


448533AL119710Hs.21365nucleosome assembly 10.5
protein 1-like 3


440684A1253123Hs.127356ESTs, Highly similar 10.3
to S21424 nestin (H


3 444017004840Hs.214neuro-oncological ventral10.3
antigen 1


438380T06430Hs.6194chondroitin sulfate 10.3
proteoglycan BEHAB/b


440471AA886146Hs.307944ESTs 10.2


413063AL035737Hs.75184chitinase 3-like 1 10.1
(cartilage glycoprote


439978BE139460Hs.124673Homo Sapiens cDNA FLJ 10
11477 fis clone HE 1


448902Zd5998Hs.22543Homo Sapiens mRNA; .
cDNA DKFZp76111912 10.1
(f


424932814070Hs.315369Homo Sapiens cDNA: 9.9
FLJ23075 fis, clone
L


431721AB032996Hs.268044KIAA1170 protein 9.9


419088A1538323Hs.52620integrin, beta 8 9.8


420602AF060877Hs.99236rogulator of G-protein8
signalling 20 9


45436511AA721252Hs.291502ESTs .
9.8


414696AF002020Hs.76918Niemann-Pick disease, 9.7
type C1


449539W80363Hs.58446ESTs g.7


412959D87458Hs.75090KIAA0282 protein 9.6


412811H06382Hs.21400ESTs 9
6


50449300A1656959Hs.222165ESTs .
9.6


426344H41821Hs.322469transcdptional activator9.5
of the c-fos p


419271N34901Hs.238532ESTs 9.5


419078M93119Hs.89584insulinoma-associated 9.4
1


451516AI800515Hs.12024ESTs 9
4


55422656AI870435Hs.1569LIM homecbox protein .
2 9.3


449318AW236021Hs.78531Homo Sapiens, Similar 9.3
to RIKEN cDNA 5730


414175AI308876Hs.103849hypotheticalprotein 9.3
DKFZp761D112


415279F04237Hs.1447glial fibdllary acidic9.2
protein


428784Y12851Hs.193470purinergic receptor 2
P2X, ligand-gated 9
io


429903AL134197Hs.93597cyclin-dependent kinase.
5, regulatory su 9.2


424641A8001106Hs.15i413glia maturation factor,9.1
beta


417435NM Hs.82129carbonic anhydrase 9.1
005181 III, muscle specific


449448D60730Hs.57471ESTs 9.1


408508A1806109Hs.135736KIAA1580 protein 9
0


452785AL359942Hs.296434erythroid differentiation.
and denucleati 9.0


448986H42169Hs.18653hypothetical protein 8.9
FLJ14627


447072D61594Hs.17279tyrosylprotein sulfotransferase8.9
1


433800A1034361Hs.135150lung type-I cell membrane-associated8.9
gly


408926AF217525Hs.49002Down syndrome cell B
adhesion molecule 8


449625NM Hs.23796adz (odd Oz/ten-m, .
014253 Drosophila) homolog 8.8
1


400292AA250737Hs.72472ESTs 8,7


417404NM Hs.82101pleckstrin homology-like8.7
007350 domain, family


420345AW295230Hs.25231ESTs 8,7


429927NM Hs.2522adenylate cyclase 8 8
001115 (brain) 7


75437528N59646Hs.169745crumbs (Drosophila) .
homolog 1 8,7


440152AB002376Hs.7006KIAA0378 protein g,7


451099852795Hs.25954intedeukin 13 receptor,8.6
alpha 2


400780 g,6


434891AA814309Hs.123583ESTs 6
8


go449277AA001064Hs.172976ESTs .
8,6


415709AA649850Hs.278558ESTs 8.5


439947ABOD6627Hs.6788astrotactin 8.5


447197836075 gb:yh88b01.si Scares 8.5
placenta Nb2HP Homo


158


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WO 03/025138 PCT/US02/29560
433042AW193534Hs.281895Homo Sapiens cDNA FLJ116608.4
fis, clone HE


416370N90470Hs.203697ES1's, Weakly similar 8.4
to 138022 hypotheti


452786861362Hs.106642ESTs, Weakly similar 8.4
to T09052 hypotheti


415796887548Hs.78854ATPase, Na+/K+bansporfing,8.3
beta 2 poly


426271AF026547Hs.169047chondroitin sulfate 8.3
protecglycan 3 (near


408947AL080093Hs.49117Homo Sapiens mRNA; 8.3
cDNA DKFZp564N1662
(f


419863AW952691Hs.93485Homo Sapiens mRNA; 8.3
cDNA DKFZp761 D191
(fr


433447029195Hs.3281neuronal pentraxin 8.3
II


431467N71831Hs.256398Homo Sapiens mRNA; 8.3
cDNA DKFZp434E0528
(f


1 409327L41162Hs.53563collagen, type IX, 8.3
~ alpha 3


414300AI304870Hs.188680ESTs 8.2


407728AW071502Hs.175931ESTs 8.2


422798892347Hs.34574ESTs, Weakly similar 8.2
to ALUt HUMAN ALU
S


419704AA429104Hs.45057ESTs 8.2


15 429007D80642 gb:HUM092E09B Human 8.1
fetal brain (TFujiwa


442710A1015631Hs.23210ESTs 8.1


425048H05468Hs.i64502ESTs 8.1


429149AW193360Hs.197962ESTs, Weakly similar 8.0
io 138022 hypothe6


445740T78281Hs.13226Homo sapiens clone 8.0
25181 mRNA sequence


418771AA807881Hs.25329ESTs 7.9


422728AW937826Hs.103262ESTs, Weakly similar 7.9
to ZN91 HUMAN ZINC


425984AW836277Hs.165636hypolhefical protein 7.9
DKFZp761 C07121


448408AA322866Hs.21i07neuroligin 7.9


455364H72176Hs.4273hypothetical protein 7.9
FLJ13159


25 446619AUD76643Hs.313secreted phosphoprotein7.9
1 (osteoponfin,


435501AW051819Hs.129908KIAA0591 protein 7.8
,


423600AI633559Hs.310359ESTs 7.8


450625AW970107 gb:EST382188 MAGE resequences,7.8
MAGK Homo


415314N88802Hs.5422glycoprotein M6B 7.7


30 420036860336Hs.52792Homo Sapiens mRNA; 7.7
cDNA DKFZp58611823
(f


427687AW003867Hs.1570histamine receptor 7.7
H1


449328AI962493Hs.197647ESTs 7.7


419249X14767Hs.89768gamma-aminobutyric 7.7
acid (GAGA) A recepto


407896D76435Hs.41154Zic family member 1 7.7
(odd-paired Drosophi


35 419103240229Hs.96423hypothetical protein 7.6
FLJ23033


438779NM-003787Hs.6414nucleolar protein 4 7.6


433532AW975367 gb:EST387475 MAGE resequences,7.6
MAGN Homo


448555AI536697Hs.159863ESTs 7.5


439662H97552Hs.269060ESTs 7.5


40 448543AW897741Hs.21380Homo Sapiens mRNA; 7.5
cDNA DKFZp586P1124
(f


410099AA081630Hs.169387KIAA0036 gene product 7.5


431592869016Hs.213194hypothetical protein 7.4
MGC10895


409731AA125985Hs.56145thymosin, beta, idenfified7.4
in neuroblast


405819 7.4


45 407886AW969688Hs.100826ESTs 7.4


437416AL359605Hs.283851Homo Sapiens mRNA; 7.4
cDNA DKFZp547G036
(fr


437698861837Hs.7990ESTs, Moderately similar7.4
to 184505 calci


408604D51408Hs.21925ESTs 7.4


418506AA084248Hs.85339G protein-coupled receptor7.3
39


447499AW262580Hs.147674protocadherin beta 7.3
16


454036AA374756Hs.93560Homo Sapiens mRNA for 7.3
KIAA1771 protein,


409746NM Hs.56294RAB33A, member RAS 7.2
004794 oncogene family


410037A8020725Hs.58009KIAA0918 protein 7.2


419318AW969742Hs.291005ESTs 7.2


424051AL110203Hs.13B411Homo Sapiens mRNA; 7.2
5 cDNA DKFZp586J 1922
(f


442026AI243749Hs.8074brain-specific angiogenesis7.2
inhibitor 3


448243AW369771Hs.52620integrin, beta 8 7.2


436281AW411194Hs.85195myeloid leukemia factor7.2
1


426429X73114Hs.169849myosin-binding protein7.2
C, slow-type


407182AA312551Hs.230157ESTs 7.1


415293849462Hs.106541ESTs 7.1


422764AI767727Hs.47522ESTs 7.1


451592AI805416Hs.213897ESTs 7.1


429469M64590Hs.27glycine dehydrogenase(decarboxylafing;7.0


65 415734NM Hs.78748KIAA0237 gene product 7.0
014747


434149243829Hs.19574hypothetical protein 7.0
MGC5469


436726AA324975Hs.128993ESTs, Weakly similar 7.0
to T00079 hypotheti


417632820655lis.5422glycoprotein M6B 7.0


422421AA325138Hs.235873hypotheficalprotein 6.9
FLJ22672


70 435267N23797Hs.110114ESTs 6.9


437117AL049256Hs.122593ESTs 6.9


445523230118Hs.293788ESTs, Moderately similar6.9
to unnamed prot


445900AF070526Hs.13429Homo Sapiens clone 6.9
24787 mRNA sequence


445745A8007924Hs.13245KIAA0455 gene product 6.9


75 424085NM Hs.139226replicafion factor 6.9
002914 C (activator 1) 2
(40


428588F12101Hs.185701Homo Sapiens mRNA full6.8
length insert cDN


421723AA620400Hs.300717sodium channel, voltage-gated,6.8
type III,


447342A1i99268Hs.19322Homo Sapiens, Similar 6.7
to RIKEN cDNA 2010


443297A1049864Hs.133029ESTs 6.7


go 443992AW022228Hs.322922ESTs 6.7


453096AW294631Hs.11325ESTs 6.7


453857AL080235Hs.35861DKFZP586E1621 protein 6.7


443761AI525743Hs.160603ESTs 6.6


159


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
429609AF002246Hs.210863cell adhesion molecule6.6
with homology to


435056AW023337Hs.5422glycoprotein M6B 6.5


453431AF094754Hs.32973glycine receptor, beta6.5


444190AI878918Hs.10526cysteine and glycine-rich6.5
protein 2


418110843523Hs.217754hypotheticalprotein 6.5
FLJ22202


413988M81883Hs.324784glutamate decarboxylase6.5
1 (brain, 67kD)


420805L10333Hs.99947. reticulon 1 6.4


429125AA446854Hs.271004ESTs, Weakly similar 6.4
to 138022 hypotheti


435256AF193766Hs.13872cytokine-like protein 6.4
C17


407866AW088232Hs.89506paired box gene 6 (aniddia,6.3
keratitis)


440700AW952281Hs.296184guanine nucleotide 6.3
binding protein (G
pr


427701AA411101Hs.243886nuclear autoantigenic 6.3
sperm protein (his


422949AA319435 gb:EST21657 Adrenal 6.2
gland tumor Homo sap


445102AW204610Hs.22270ESTs 6.2


452401NM Hs.29352tumor necrosis factor,6.2
007115 alpha-induced pro


435538AB011540Hs.4930low density lipoprotein6.2
receptor-related


410102AW248508Hs.279727Homo Sapiens cDNA FLJ140356.2
fis, clone HE


416871H98716 gb:yx13d08.s1 Soares 6.1
melanocyte 2NbHM Ho


416702AA186428Hs.85591ESTs 6
1


419347C15944Hs.90005superiorcervical ganglia,.
neural specifi 6.1


424997AL138167Hs.96920ESTs 6.1


438660U95740Hs.6349Homo Sapiens, clone 6.1
IMAGE:3010666, mRNA,


453649Y07494Hs.34114ATPase, Na+IK+transporting,6.1
alpha 2 (+)


449444AW818436Hs.23590solute carrier family 6.1
16 (monocarboxylic


414117W88559Hs.1787proteolipid protein 6.0
1 (Pelizaeus-Meabac


425517AF121179 gb:AF121179 Homo Sapiens6.0
liver (Chang L-


427457AW779105Hs.164682ESTs 6.0


437034AA742643 gb:ny91c01.s1 NCI_CGAP-GCB16.0
Homo Sapiens


444170AW613879Hs.102408ESTs 6.0


457183H91882Hs.118569Dvl-binding protein 6.0
IDAX (inhibition of


448999AF179274Hs.22791transmembrane protein 6.0
with EGF-like and


454048H05626Hs.6921ESTs 6.0


439772AL365406Hs.10268Homo Sapiens mRNA full5.9
length insert cDN


448944AB014605Hs.22599atrophin-1 interacting5.9
protein 1; activi


410011AB020641Hs.57856' PFTAIRE protein kinase5.9
1


415486H12214Hs.13284ESTs, Weakly similar 5.9
to 2109260A B cell


438993AA828995 gb:od77b08.s1 NCI-CGAP_Ov25.9
Homo Sapiens


447350AI375572Hs.172634ESTs 5.9


451783842554Hs.210862T-box, brain, t 5
9


447101N72185Hs.44189ESTs .
5.9


440492839127Hs.21433hypothetical protein 5.9
DKFZp547J036


440274824595Hs.7122scrapie responsive 5.9
protein 1


438461AW075485Hs.286049phosphosedne aminotransferase5.9


418064BE387287Hs.83384S100 calcium-binding 5.8
protein, beta (neur


437036AI571514Hs.133022ESTs 5.7


412225AW902042 gb:OVO-NN1022-170400-193-c025.7
NN1022 Homo


426342AF093419Hs.169378multiple PDZ domain 5.7
protein


444218AF070641Hs.10684Homo Sapiens clone 5.7
24421 mRNA sequence


445828F05802Hs.81907ESTs 5
7


447198D61523Hs.283435ESTs .
5.7


427897NM Hs.303084apelin; peptide ligand5.7
017413 for APJ receptor


448499BE613280Hs.77550hypothetical protein 5.7
MGC1780


443672AA323362Hs.9667butyrobetaine (gamma),5.6
2-oxoglutarate dl


412155838167Hs.12449Homo Sapiens transmembrane5.6
protein HTMP1


435718806569Hs.269534'ESTs 5.6


449340AW235786Hs.195359hypothetical protein 5.6
MGC10954


424481819453Hs.1787proteolipid protein 5.6
1 (Pelizaeus-Meabac


451996AW514021Hs.245510ESTs 5.6


422411AW749443Hs.22511ESTs 5
6


438328AI492261Hs.32450ESTs .
5.6


433244AB040943Hs.271285KIAA1510 protein 5.6


435191815912Hs.4817Homo Sapiens clone 5.5
24461 mRNA sequence


418677S83308Hs.87224SRY (sex determining 5.5
region Y)-box 5


400859 5.5



413625AW451103Hs.71371ESTs 5.5


421863AI952677Hs.108972Homo Sapiens mRNA; 5.5
cDNA DKFZp434P228
(fr


434933891095Hs.4276KIAA1701 protein 5.5


438702A1879064Hs.54618ESTs 5.5


452055AI377431Hs.141693hypothetical protein 5.5
MGC10858


430979AI479755Hs.129010ESTs 5.5


412709AL022327Hs.74518KIAA0027 protein 5.5


439920H05430Hs.288433neurotrimin 5.5


424343AW956360Hs.4748adenylate cyclase activating5.d
polypeptide


407846AA426202Hs.40403Cbp/p300-interacting 4
transactivator 5
wit


419235AW470411Hs.288433, .
neurotrimin 5.4


4180308E207573Hs.83321neuromedin B 5.4


410330AW023630Hs.46786ESTs 5.4


410781A1375672Hs.165028ESTs 5.4


420658AW965215Hs.336656ESTs 5
4


g0 421308AA687322Hs.192843leucine zipper protein.
FKSG14 5.4


443740856434Hs.21062ESTs 5.4


426457AW894667Hs.169965chimerin (chimaerin) 5.4
1


450375AA009647Hs.8850a disintegdn and metalloproteinase5.4
doma


160


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412494AL133900Hs.792ADP-ribosylation factor5.4
domain protein 1


426600NM Hs.171014VGF nerve growth factor5.4
003378 inducible


424432A8037821Hs.146858protocadhedn 10 5.4


429250H56585Hs.198308lryptophan rich basic 5.4
protein


443785AW449952Hs.190125basic-helix-loop-helix-PAS5.4
protein


436282891913Hs.272104ESTs, Moderately similar5.4
to ALU1 HUMAN A


404584 5.3


430091AB032958Hs.233023KIAA1132 protein 5.3


439845AL355743Hs.56663Homo Sapiens EST from 5.3
clone 41214, full


1 424001W67883Hs.137476paternally expressed 5.3
~ 10


425073W39609Hs.22003solute carrier family 5.3
6 (neurotransmitte


426625T78300Hs.300642serologically defined 5.3
colon cancer antig


428137AA421792Hs.170999ESTs 5.3


428679AA43t765 gb:zw80c03.s1 Soares 5.3
iestis_NHT Homo sap


1 438176AW138970Hs.122113ESTs 5.3



440138A8033023Hs.318127hypotheticalprotein 5.3
FLJ10201


451018AW965599Hs.247324mitochondrial ribosomal5.3
protein 514


416340N31772Hs.79226fasciculation and elongation5.3
protein zet


435244N77221Hs.187824ESTs 5.3


446035NM Hs.135655am68-like phosphotyrosine5.3
006558 protein, T-ST


424624AB032947Hs.151301Ca21-dependent activator5.3
protein for sec


407748AL079409Hs.38176KIAA0606 protein; SCN 5.3
Circadian Oscillat


430437AI768801Hs.169943Homo Sapiens cDNA FLJ 5.3
13569 fis, clone PL


414825X06370Hs.77432epidermal growth factor5.2
receptor (avian


25 453941039817Hs.36820Bloom syndrome 5.2


424998058515Hs.154138chitinase 3-like 2 5.2


423419855336Hs.23539ESTs 5.2


424922BE386547Hs.217112hypothetical protein 5.2
MGC10825


447359NM Hs.18268adenylate kinase 5 5.2
012093


3 406206AF041853Hs.43670kinesin family member 5.2
0 3A


421013M62397Hs.1345mutated in colorectal 5.2
cancers


429443AB028967Hs.202687potassium voltage-gated5.2
channel, Shal-re


434367A8020700Hs.3830KIAA0893 protein 5.2


444861846789Hs.76118ubiquitin carboxyl-terminal5.2
esterase L1


35 446142AI754693Hs.145968ESTs 5.2


448816A8033052Hs.22151KIAA1226 protein 5.2


451050AW937420Hs.69662ESTs 5.2


451106BE382701Hs.25960v-myc avian myelocytomatosis5.2
viral relal


439285AL133916Hs.172572hypothetical protein 5.2
FLJ20093


416737AF154335Hs.79691LIM domain protein 5.2


424800AL035588Hs.153203MyoD family inhibitor 5.2


443695AW204099Hs.337720ESTs, Weakly similar 5.2
to AF1267801 retin


415257F03016Hs.27513ESTs 5.2


433929A1375499Hs.27379ESTs 5.1


45 415651A1207162Hs.3815stathmin-like-protein 5.1
883


451027AW519204Hs.40808ESTs 5.1


409172299399Hs.118145ESTs 5.1


423343AA324643Hs.246106ESTs 5.1


429172AA447417Hs.285491ESTs 5.1


437268AI754847Hs.227571regulator of G-protein5.1
signalling 4


451270AW341392Hs.235795ESTs 5.1


452904AL157581Hs.30957Homo Sapiens mRNA; 5.1
cDNA DKFZp434E0626
(f


420560AW207748Hs.59115ESTs 5.1


418097845137Hs.21868ESTs 5.1


S 442910A1365130Hs.11307ESTs, Weakly similar 5.1
5 to T19326 hypotheti


434849AW292765Hs.8053ESTs 5.1


413554AA319146Hs.75426secretograninll(chromogranin5.1
C)


414217A1309298Hs.279898Homo Sapiens cDNA: 5.1
FLJ23165 tis, clone
L


41.2068572043Hs.73133metallothionein 3 (growth5.0
inhibitory fac


6~ 413627BE182082Hs.246973ESTs 5.0


418661NM Hs.i E2F transcription factor5.0
001949189 3


422438AA445925Hs.270896ESTs, Moderately similar5.0
to 2195 HUMAN Z


423728AW891294Hs.132136solute tarter family 5.0
4, sodium bicarbon


431431AL096711Hs.252953Human DNA sequence 5.0
from clone RP3-403A15


65 435087AW975241Hs.23567ESTs 5.0


452097A8002364Hs.27916a disintegrin-like 5.0
and metalloprotease
(


410434AF051152Hs.63668toll-like receptor 4.9
2


408692AL040127Hs.34074dipeptidylpeptidaseVl 4.9


407808AA663559Hs.279789histone deacetylase 4.9
3


7~ 418940H17739Hs.288513Human DNA sequence 4.9
from clone RP5-899C14


425977815138Hs.165570Homo Sapiens clone 4.9
25052 mRNA sequence


426814AF036943Hs.172619myelin transcription 4.9
factor 1-like


447112H17800Hs.7154ESTs 4.9


449574F05048Hs.175373ESTs 4.9


75 453652AW009640Hs.28368ESTs, Moderately similar4.9
to S65657 alpha


423869BE409301Hs.134012C1q-relatedtactor 4.9


413248T64858Hs.21433hypothetical protein 4.9
DKFZp547J036


449176A1633545Hs.198072ESTs 4.9


448451AW015994 gb:Ul-H-BIOp-abh-g-09-0-ULs14.8
NCI_CGAP_S


402604 4.8


436039AW023323Hs.121070ESTs 4.8


448769N66037Hs.38173ESTs 4.8


423678AW963357Hs.7847ESTs 4.8


161


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439451AF086270Hs.278554heterochromatin-like 4.8
protein 1


425870813406Hs.56782ESTs 4.8


408777U71204Hs.47626Ric (Drosophila)-like,4.8
expressed in neur


413409AI638418Hs.78580DEADIH (Asp-Glu-Ala-AspIHis)4.8
box polypep


413623AA825721Hs.246973ESTs 4.8


417246AI760098Hs.21411ESTs 4.8


420900AL045633Hs.44269ESTs 4.8


424153AA451737Hs.141496MAGE-like 2 4.8


443539A1076182Hs.134074ESTs, Moderately similar4.8
to ALU6_HUMAN A


1 448750U95020Hs.21903calcium channel, voltage-dependent,4.8
o beta


454030AW021429Hs.231980ESTs 4.8


424458M29273Hs.1780myelin associated 4.8
glycoprotein


444119841231Hs.184261ESTs, Weakly similar 4.8
to T26686 hypothe6


407792A1077715Hs.39384putative secreted 4.8
ligand homologous
to f


1 431462AW583672Hs.256311granin-like neuroendocrine4.7
S peptide precu


431103M57399Hs.44pleiotrophin (heparin4.7
binding growth fac


429956AI374651Hs.22542ESTs 4.7


435060A1422719Hs.233349ESTs, Weakly similar 4.7
to fork head like
p


436203BE384982Hs.5076Homo sapiens cDNA: 4.7
FLJ22128 fis, clone
H


20 4484758E613134Hs.247474hypothetical protein 4.7
FLJ2i032


422222A1699372Hs.193247hypotheticalprotein 4.7
DKFZp434A171


431733AW298410Hs.21475ESTs 4.7


449353AA001220Hs.271369ESTs 4.7


452022AW072330Hs.293875ESTs 4.7


25 454269AI961060Hs.129908KIAA0591 protein d.7


404541 4.7


428189AA424030Hs.46627ESTs 4.7


409125817268Hs.259673axonal transport of 4.7
synaptic vesicles


458435AI418718Hs.144121ESTs, Weakly similar 4.6
to T46916 hypothefi


425745U44060Hs.14427Homo Sapiens cDNA: 4.6
FLJ21800 fis, clone
H


413492D87470Hs.75400KIAA0280 protein 4.6


419629AB020695Hs.91662KIAA0888 protein 4.6


407638AJ4D4672Hs.334483hypolhefical protein 4.6
FLJ23571


436140W87355Hs.269587ESTs 4.6


35 439169AI912122Hs.41095ESTs 4.6


443150A1034467Hs.34650ESTs 4.6


451073AI758905Hs.206063ESTs 4.6


451659BE379761Hs.14248ESTs 4.6


452106AI141031Hs.21342ESTs 4.6


40 451407AA131376Hs.326401fibroblast growth 4.6
factor 12B


448765815337Hs.21958Homo Sapiens mRNA; 4.6
cDNA DKFZp547D086
(fr


430147860704Hs.234434hairylenhancer-of-split4.6
related with YRP


437204AL110216Hs.12285ESTs, Weakly similar 4.6
to 155214 salivary


431117AF003522Hs.250500delta (Drosophila)-like4.5
1


45 422175N79885Hs.6382ESTs, Highly similar 4.5
to T00391 hypotheti


407889834556Hs.30800ESTs, Weakly similar 4.5
to S65657 alpha-1
G


419343AA456245Hs.85603down-regulated by 4.5
Ctnnbl, a


421790AW896201Hs.22654sodium channel, voltage-gated,4.5
type I, a


429399AA452244Hs.16727ESTs 4.5


450149AW969781Hs.132863Zic family member 4.5
0 2 (odd-paired Drosophi


453118AW195849Hs.252757ESTs 4.5


443455A8001025Hs.9349ryanodine receptor 4.4
3


442613A1004002Hs.130522Kv channel-interacting4.4
protein 1


429643AA455889Hs.167279FYVE-finger-containing4.4
Rab5 effector pro


5 416209AA236776Hs.79078MAD2 (mitotic arrest 4.4
5 deficient, yeast,
h


418845AA852985Hs.89232chromobox homolog 4.4
5 (Drosophila HP1
alph


435202AI971313Hs.170204KIAA0551 protein 4.4


437496AA452378Hs.170144Homo Sapiens mRNA; 4.4
cDNA DKFZp547J125
(fr


451254AI571016Hs.172967ESTs 4.4


439039A1656707Hs.48713ESTs 4.4


439979AW600291Hs.6823hypothetical protein 4.4
FLJ10430


441607NM Hs.7912neuronal cell adhesion4.4
005010 molecule


424983AI742434Hs.169911ESTs 4.4


410611AW954134Hs.20924KIAA1628 protein 4.4


65 402605 4.4


409248AB033035Hs.51965KIAA1209 protein 4.4


442222A1061301Hs.i64773ESTs 4.4


454027840192Hs.21527Human DNA sequence 4.4
from clone G51-115M3


454293H49739Hs.134013ESTs, Moderately similar4.4
to HK61_HUMAN H


7~ 442632AW206560Hs.253569ESTs 4.4


407304AA565832 gb:nj32b03.s1 NCI_CGAP_AA14.4
Homo Sapiens


423279AW959861Hs.290943ESTs 4.3


427194AA399018Hs.250835ESTs 4.3


419723AL120193Hs.92614longevity assurance 4.3
(LAG1, S. cerevisiae


75 445810AW265700Hs.155660ESTs 4.3


409734BE161664Hs.56155hypothetical protein 4.3


410389AW954049Hs.8177ESTs, Weakly similar 4.3
to PIHUB6 salivary


411571AA122393Hs.70811hypotheficalprotein 4.3
FLJ20516


433024AA573847Hs.26549KIAA1708 protein 4.3


453202AW085781Hs.26270hypothefical protein 4.3
FLJ11588


425264AA353953Hs.20369ESTs, Weakly similar 4.3
to gonadotropin ind


416427BE244050Hs.79307RacICdc42 guanine 4.3
exchangefactor(GEF)


431789H19500Hs.269222mitogen-activated 4.3
protein kinase 4


162


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444600841398Hs.6996ESTs 4.3


454042H22570Hs.172572hypothetical protein 4.3
FLJ20093


441899AI372588Hs.8022TU3A protein 4.3


425256BE297611Hs.155392collapsin response 4.3
mediator protein 1


410358AW975168Hs.13337ESTs, Weakly similar 4.2
to unnamed protein


430291AV660345Hs.23B126CGI-49 protein 4.2


433597AA70B205Hs.100343ESTs 4.2


444127N63620Hs.13281ESTs 4.2


448507AL133109Hs.21333Homo Sapiens mRNA; d.2
cDNA DKFZp566N1047
(f


413589AW452631Hs.313803ESTs, Highly similar 4.2
to AF1578331 noncl


408577H50572Hs.19515ESTs, Highly similar 4.2
to NRG3-HUMAN PRO-N


409719AI769160Hs.108681Homo Sapiens brain 4.2
tumor associated prot


428536A1i43139Hs.2288visinin-like 1 4.2


429118H20669Hs.35406ESTs, Highly similar 4.2
to unnamed protein


432865AI753709Hs.152484ESTs, Weakly similar 4.2
to 138022 hypotheG


447138AI439112Hs.93828ESTs, Weakly similar 4.2
to 2109260A B cell


450648AI703366Hs.26766ESTs 4.2


451459A1797515Hs.270560ESTs, Moderately similar4.2
to ALU7-HUMAN A


421686A8011156Hs.106794KIAA0584 protein 4.2


452776AA194540Hs.13522ESTs, Weakly similar 4.2
to 138022 hypolhefi


436421A1678031Hs.122813ESTs, Weakly similar 4.2
to ZN22 HUMAN ZINC


423858AL137326Hs.133483Homo Sapiens mRNA; 4.2
cDNA DKFZp434B0650
(f


434001AW950905Hs.3697serine (or cysteine) 4.2
proteinase inhibito


437380AL359577Hs.112198Homo Sapiens mRNA; 4.2
cDNA DKFZp547M073
(fr


432328AI572739Hs.1954716-phosphofructo-2-kinaselfructose-2,6-bi4.1


439607BE540565Hs.159460ESTs 4.1


424028AF055084Hs.153692Homo Sapiens cDNA FLJ143544.1
fis, clone Y7


446936H70207Hs.d7314ESTs 4.1


424240A8023185Hs.143535calciumlcalmodulin-dependent4.1
protein kin


3~ 412446AI7680i5Hs.92127ESTs 4.1


409953AA332277Hs.57691cadherin 18, type 2 4.1


416220N49776Hs.170994hypotheficalprotein 4.1
MGC10946


419683AA248897Hs.48784ESTs 4.1


426071AW138057Hs.163835ESTs 4.1


428743AL080060Hs.301549Homo Sapiens mRNA; d.1
cDNA DKFZp564H172
(fr


432809AA565509Hs.131703ESTs 4.1


440105AA694010Hs.6932Homo sapiens clone 4.1
23809 mRNA sequence


452039AI922988Hs.172510ESTs 4.1


425905AB032959Hs.318584novel C3HC4 type Zinc 4.1
finger (ring finge


457561AA331517Hs.286055chimerin (chimaerin) 4.1
2


429038AL023513Hs.194766seizure related gene 4.1
6 (mouse)-like


433932AW954599Hs.169330neuronal protein 4.1


436637AI783629Hs.26766ESTs 4.1


439231AW581935Hs.141480Homo Sapiens mRNA; 4.1
cDNA DKFZp434N079
(fr


450530NM Hs.25121cytochrome P450, subfamily4.1
006668 46 (cholester


407721Y12735Hs.38018dual-specificity tyrosine-(Y)-phosphoryl4.1


407881AW072003Hs.40968heparan sulfate (glucosamine)4.1
3-0-sulfot


410486AW235094Hs.69233zinc finger protein 4.0


413916N49813Hs.75615apolipoprotein GII 4.0


438703A1803373Hs.31599ESTs 4.0


424726AK001007Hs.138760Homo sapiens cDNA FLJ101454.0
fis, clone HE


405771 4.0


418841NM Hs.89137low density lipoprotein-related4.0
002332 protefi


421764AI6B1535Hs.148135serinellhreonine kinase4.0
33


424176AL137273Hs.142307hypothetical protein 4.0


425773N21279Hs.237749ESTs 4.0


427304AA761526Hs.163853ESTs 4.0


428882AA436915Hs.131748ESTs, Moderately similar4.0
to ALU7_HUMAN A


452834AI638627Hs.105685KIAA1688 protein 4.0


453745AA952989Hs.63908hypothefical protein 4.0
MGC14726


405239089281Hs.11958oxidative 3 alpha hydroxysteroid4.0
dehydro


413801M62246Hs.35406ESTs, Highly similar 4.D
to unnamed protein


429698AI6B5086Hs.26339ESTs, Weakly similar 4.0
to 521348 probable


435854AJ278120Hs.4996putative ankyrin-repeat4.0
containing prote


439199840373Hs.26299ESTs 4.0


439450851613Hs.125304ESTs 4.0


446782A1653048Hs.144006ESTs 4.0


419687A1638859Hs.227699ESTs, Weakly similar 3.9
to T2D3_HUMAN TRANS


402408 3.9


7~ 453362H14988Hs.107375ESTs 3.9


414219W20010Hs.75823ALL1-fused gene from 3.9
chromosome 1q


420578AA813546Hs.99034GTP-binding protein 3.9
Rho7


425010T16837Hs.4241ESTs 3.9


444230H95537Hs.146067ESTs 3.9


441736AW292779Hs.169799ESTs 3.9


418951F07809Hs.89506paired box gene 6 (aniridia,3.9
keratitis)


406311 3.9


408460AA054726Hs.285574ESTs 3.9


410658AW105231Hs.192035ESTs 3.9


414699A1815523Hs.76930synuclein, alpha (non 3.9
A4 component of am


418849AW474547Hs.53565Homo Sapiens PIG-M 3.9
mRNA for mannosyltran


429477AI275514Hs.6658ESTs 3.9


433766AA609234Hs.1i2669ESTs 3.9


163


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436190AK001059 gb:Homo Sapiens cDNA 3.9
' FLJ10197 fis, clone


447891841754Hs.6496ESTs 3.9


450221AA328102Hs.24641cytoskeleton associated3.9
protein 2


404283 3~9


453919AW959912Hs.7076KIAA1705 protein 3.9


429656X05608Hs.211584neurofilament, light 3.9
polypeptide (68kD)


412754AW160375Hs.74565amyloid beta (A4) 3.9
precursor-like protein


445314AIfi89948Hs.65489Homo Sapiens cDNA: 3.9
FLJ21517 fis, clone
C


435652N32388Hs.334370uncharacterized hypothalamus3.9
protein HBE


1 407378AA299264Hs.57776ESTs, Moderately similar3.9
~ to 138022 hypot


438054AA776626Hs.62183ESTs 3.9


436420AA443966Hs.31595ESTs 3.9


445133AW157646Hs.153506ESTs 3.9


432590AI609273Hs.110783ESTs 3.9


15 453331AI240665Hs.8895ESTs 3.9


410227AB009284Hs.61152exostoses (multiple)-like3.8
2


424635AA420687Hs.i Homo sapiens cDNA 3.8
15455FLJ14259 fis, clone
PL


451489NM Hs.26468amyloid beta (A4) 3.8
005503 precursor protein-bind


447247AW369351Hs.287955Homo Sapiens cDNA 3.8
FLJ13090 fis, clone
NT


448302AI480208Hs.182906Homo Sapiens mRNA 3.8
for KIAA1872 protein,


415669NM-005025Hs.78589serine (or cysleine) 3.8
proteinase inhibito


417355D13168Hs.82002endothelin receptor 3.8
type B


446727AB011095Hs.16032KIAA0523 protein 3.8


424340AA339036Hs.7033ESTs 3.8


25 423346A1267677Hs.127416synaptojanin 1 3.8


412788AA120960Hs.198416ESTs 3.8


404593 3.8


416856N27833Hs.269028ESTs, Weakly similar 3.8
to 138022 hypothe6


429896AA460367Hs.224223ESTs, Moderately similar3.8
to 138022 hypot


439619AW975998Hs.58595ESTs, Weakly similar 3.8
to 138022 hypotheti


439634W79377Hs.167microtubule-associated3.8
protein 2


440322AA879430 gb:oj91dO8.s1 Soares_NFL-T-GBC_Si3.8
Homos


447761AF061573Hs.19492protocadherin 8 3.8


452453AI902519 gb:OV-BT009-101198-0513.8
BT009 Homo sapien


35 439671AW162840Hs.6641kinesinfamilymemberSC3.8


447937AL109716Hs.20034Homo Sapiens mRNA 3.8
full length insert
cDN


459278AW294659Hs.34054Homo Sapiens cDNA: 3.8
FLJ22488 fis, clone
H


447028AI973128Hs.167257brain link protein-1 3.8


449458AI805078Hs.208261ESTs 3.8


4~ 445888AF070564Hs.13415Homo Sapiens clone 3.8
24571 mRNA sequence


407385AA610150Hs.272072ESTs, Weakly similar 3.8
to 138022 hypotheti


428841AI418430Hs.104935ESTs 3.8


430643AW970065Hs.287425MEGF10 protein 3.8


422263AA307639Hs.129908KIAA0591 protein 3.8


45 451625856793Hs.106576alanine-glyoxylate 3.8
aminotransferase
2-li


439236BE160952Hs.247117ESTs, Moderately similar3.8
to ALUF-HUMAN !


441928AI370188Hs.211454ESTs 3.8


441797AI936933Hs.214635ESTs 3.7


414922D00723Hs.77631glycine cleavage system3.7
protein H (amino


425588F07396Hs.46751ESTs 3.7


437007AA741300Hs.202599ESTs, Weakly similar 3.7
to 138022 hypotheti


435793A8037734Hs.4993KIAA1313 protein 3.7


443682AI383061Hs.47248ESTs,HighlysimilartosimilartoCdcl43.7


425741AF052152Hs.159412Homo Sapiens clone 3.7
24628 mRNA sequence


418211BE244746Hs.247474hypotheticalprotein 3.7
FLJ21032


440080AW051597Hs.143707ESTs 3.7


452898AA814497Hs.78792ESTs 3.7


435575AF213457Hs.44234triggering receptor 3.7
expressed on myeloid


409234AI879419Hs.2720fiESTs 3.7


420489AA815089Hs.193513ESTs 3.7


426890AA393167Ns.41294ESTs 3.7


438849W28948Hs.10762ESTs 3.7


441869NM Hs.8004huntingtin-associated3.7
003947 protein interactin


448796AA147829Hs.301431endothelial zinc finger3.7
protein induced


65 459318NM gb:Homo sapiens adenomatosis3.7
000038 polyposis c


459518AI937419Hs.294069Homo Sapiens cDNA 3.7
FLJ 13384 fis, clone
PL


434444AI765276Hs.101257hypothetical protein 3.7
MGC3295


421183AL135740Hs.102447TSG22-like 3.7


410555U92649Hs.64311a disintegrin and 3.7
metalloproteinase
doma


70 421637AF035290Hs.106300Homo Sapiens clone 3.7
23556 mRNA sequence


418522AA605038Hs.7149Homo Sapiens cDNA: 3.7
FLJ21950 fis, clone
H


420807AA280627Hs.57846ESTs 3.7


449961AW265634Hs.133100ESTs 3.7


422634Ntv>_016010Hs.118821CGI-62 protein 3.7


75 421030AW161357Hs.101174microtubule-associated3.7
protein tau


427099A8032953Hs.173560odd Ozlten-m homolog 3.7
2 (Drosophila, mous


452355N54926Hs.29202G protein~coupled 3.7
receptor 34


440483AI200836Hs.150386ESTs 3.7


429597NM Hs.2442a disintegrin and 3.7
003816 metalloproteinase
doma


423756AA828125 gb:od71 a09.s1 NCI-CGAP-Ov23.6
Homo sapiens


425187AW014486Hs.22509ESTs 3.6


434859BE255080Hs.299315collapsin response 3.6
mediator protein-5;
C


413199M62843Hs.75236SLAV (embryonic lethal,3.6
abnormal vision,


164


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445729H21066Hs.13223Homo Sapiens mRNA 3.6
full length insert
cDN


416120H46739 gb:yo14h02.s1 Snares 3.6
adult brain N2b5HB5


429239AA448419Hs.45209ESTs 3.6


419086NM Hs.89591Kallmann syndrome 3.6
000216 1 sequence


446659AI335361Hs.226376ESTs 3.6


426757AW205640Hs.158206ESTs 3.6


418819AA228776Hs.191721ESTs ~ 3.6


458332A1000341Hs.220491ESTs 3.6


408826AF216077Hs.48376Homo Sapiens clone 3.6
HB-2 mRNA sequence


1 410343AA084273Hs.76561ESTs, Weakly similar 3.6
~ 1c S47072 finger
pr


410507AA355288Hs.40834transifional epithelia3.6
response protein


422977AA631498 gb:np83h04.s1 NCI 3.6
CGAP Thy1 Homosapiens


425305AA363025Hs.155572Human clone 23801 3.6
mRNA sequence


428002AA418703 gb:zv98c03.s1 Soares_NhHMPu3.6
S1 Homo sapi


15 428505AL035461Hs.2281chromogranin B (secretogranin3.6
1)


430530AA480870Hs.47660ESTs 3.6


4311425A1913146Hs.318725CGI-72 protein 3.6


438078A1016377Hs.131693ESTs 3.6


442927A1024347Hs.131519ESTs 3.6


446242N66336Hs.7360ESTs 3.6


448831AL080123Hs.22182zinc finger protein 3.6
23 (KOX 16)


450474AW872844Hs.201919ESTs 3.6


452198A1097560Hs.61210ESTs, Weakly similar 3.6
to 138022 hypotheti


455800822479Hs.167073Homo Sapiens cDNA 3.6
FLJ13047 fis, clone
NT


25 436443AW138211Hs.128746ESTs 3.6


426514BE616633Hs.170195bone morphogenetic 3.6
protein 7 (osteogenic


456038AA203285Hs.294141ESTs, Weakly similar 3.6
to alternatively
sp


d08902AW014869Hs.5510ESTs 3.6


442950AI500417Hs.46764ESTs 3.6


423905AW579960Hs.135150lung type-I cell membrane-associated3.6
gly


425478A8007953Hs.268840ESTs 3.6


453884AA355925Hs.36232KIAA0186 gene product3.6


404721 3.6


408453A1369838Hs.45i27chondroitin sulfate 3.6
proteoglycan 5 (neur


3 440553AA889416Hs.295362Homo Sapiens cDNA 3.5
FLJ14459 fis, clone
HE


446372A80206d4Hs.14945long fatty acyl-CoA 3.5
synthetase 2 gene


413999N46124Hs.34460ESTs 3.5


421458NM_003654Hs.104576carbohydrate (keratan3.5
sulfate Gal-6) sul


425017AL119305Hs.288405ESTs 3.5


435958H98180Hs.117975ESTs 3.5


415101845531Hs.144534ESTs 3.5


451320AW118072Hs.89981diacylglycerol kinase,3.5
zeta (104kD)


430290AI734110Hs.136355ESTs 3.5


416836D54745Hs.80247cholecystokinin 3.5


45 414821M63835Hs.77424Fc fragment of IgG, 3.5
high affinity la,
re


419412AW161058Hs.90297synuclein, beta 3.5


437860AA333063Hs.279898Homo Sapiens cDNA: 3.5
FLJ23165 fis, clone
L


452689F33868Hs.284176transferrin 3.5


416661AA634543Hs.79440IGF-II mRNA-binding 3.5
protein 3


427491843279Hs.22574ESTs, Weakly similar 3.5
to 138022 hypothefi


428037N47474Hs.89230potassium intermedialelsmall3.5
conductance


444584A1i68422 gb:ok30e11.x1 Snares 3.5
NSF_F8 9W_OT-PA_P_S


408296AL117452Hs.44155DKFZP586Gi517 protein3.5


453775NM Hs.35120replication factor 3.5
002916 C (activator 1) 4
(37


55 412659AW753865Hs.74376olfactomedin related 3.5
ER localized protei


429077AB028983Hs.2352adenylate cyclase 3.5
2 (brain)


436887AW953157Hs.193235hypothetical protein 3.5
DKFZp547D155


450784AW246803Hs.d7289ESTs 3.5


446827AW451243Hs.157069ESTs 3.5


436434N50465Hs.92927putative 47 kDa protein3.5


412777AI335773Hs.270123ESTs 3.5


436476AA326108Hs.33829bHLH protein DEC2 3.5


408601047928Hs.86122protein A 3.4


429401AW296102Hs.99272ESTs, Weakly similar 3.4
to 532567 A4 protei


65 448425AI500359Hs.233401ESTs 3.4


418727AA227609Hs.94834ESTs 3.4


451729AW160725Hs.312469ESTs 3.4


435910A1084152Hs.21782ESTs, Weakly similar 3.d
1c ALU7_HUMAN ALU
S


434577837316Hs.179769Homo Sapiens cDNA: 3.4
FLJ22487 fis, clone
H


414598A1094221Hs.135150lung type-I cell membrane-associated3.4
gly


439627BE621702Hs.29076hypothefical protein 3.4
FLJ21841


413293AL047483Hs.302498 3.4
GTP-binding
protein
homologous
to
Saccha


423992AW898292Hs.137206 3.4
Homo
Sapiens
mRNA;
cDNA
DKFZp564H1663
(f


426249F05422Hs.168352 3.4
nucleoporin-like
protein
1


75 426968007616Hs.173034 3.4
amphiphysin
(Sfiff-Mann
syndrome
with
br


430388AA356923Hs.240770 3.4
nuclear
cap
binding
protein
subunit
2,
2


435061AI651474Hs.i63944 3.4
ESTs


452291AFOi Hs.28853CDC7 (cell division 3.4
5592 cycle 7, S. cerevisi


449714AB033015Hs.23941KIAA1189 protein 3.4


443392A1055821Hs.293420 3.4
ESTs


410082AA081594Hs.158311 3.4
Musashi
(Drosophila)
homolog
1


445337NM fibroneclin leucine 3.4
013280 rich transmembrane
Hs.12523 p


408493BE206854Hs.46039phosphoglycerate mutase3.4
2(muscle)


165


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432731831178Hs.287820fibronectin 1 3.4


448758A80183i1Hs.21917KIAA0768protein 3.4


432613AW081698Hs.80712KIAA0202 protein 3.4


434164AW207019Hs.148135serinelthreonine kinase3.4
33


425294AF033827Hs.155553HNK-1 sulfotransferase3.4


410108AA081659Hs.318775OSBP-related protein 3.4
6


406815AA833930Hs.288036iRNA isopentenylpyrophosphate3.d
transferas


402855 3.3


422170A1791949Hs.112432anG-Mulledan hormone 3.3


445034AW293376Hs.143659ESTs 3.3


424378W28020Hs.167988neural cell adhesion 3.3
molecule 1


423611AB011163Hs.129908KIAA0591 protein 3.3


435593888872Hs.4964DKFZP586J1624 protein 3.3


404819 3.3


436607AW661783Hs.211061ESTs 3.3


427315AA179949Hs.175563Homo Sapiens mRNA; 3.3
cDNA DKFZp564N0763
(f


452693179153Hs.48589zinc finger protein 3.3
228


454996AW850180 gb:IL3-CT0219-271099-022-C093.3
CT0219 Homo


406927M26460 gb:Homo Sapiens (clone3.3
104) refinoblasto


409045AA635062Hs.50094Homo Sapiens mRNA; 3.3
cDNA DKFZp43400515
(f


415238837780Hs.21422ESTs 3.3


417845AL117461Hs.82719Homo sapiens mRNA; 3.3
cDNA DKFZp586F1822
(f


421192AA833718Hs.204529KIAA1806 protein 3.3


426695AW118191Hs.112729ESTs 3.3


438885A1886558Hs.184987ESTs 3.3


451762AF222980Hs.26985disrupted in schizophrenia3.3
1


452103842764Hs.33965dESTs, Weakly similar 3.3
to 138022 hypotheti


453590AF150278Hs.33578KIAA0820 protein 3.3


453616NM Hs.33846dynein, axonemal, light3.3
003462 intermediate pol


457285A1038858Hs.130522Kvchannel-interacting 3.3
protein 1


436045AB037723Hs.5028DKFZP56400423 protein 3.3


437470AL390147Hs.134742hypotheficalprotein 3.3
DKFZp547D065


448520AB002367Hs.21355doublecortin and CaM 3.3
kinase-like 1


436480AJ271643Hs.87469putative acid-sensing 3.3
ion channel


432656NM Hs.3076MHC class II transactivator3.3
000246


443898AW804296Hs.9950Sec61 gamma 3.3


423582BE000831Hs.23837Homo Sapiens cDNA FLJ118123.3
fis, clone HE


445953AI612775Hs.145710ESTs 3.3


427940AA417812Hs.38775ESTs 3.3


4~ 414683S78296Hs.76888hypothefical protein 3.3
MGC12702


428484AF104032Hs.184601salute carrier family 3.3
7 (cationic amino


420649AI866964Hs.124704ESTs, Moderately similar3.3
to S65657 alpha


419498AL036591Hs.20887hypothetical protein 3.3
FLJ10392


457579A8030816Hs.36761HRAS-like suppresser 3.3


436556AI364997Hs.7572ESTs 3.2


424369887622Hs.26714KIAA1831 protein . 3.2


457065AI476318Hs.192480ESTs 3.2


440210AW674562Hs.125296ESTs 3.2


444513AL120214Hs.7117glutamate receptor, 3.2
ionotropic, AMPA 1


434353AA630863Hs.131375ESTs, Moderately similar3.2
to ALUB HUMAN !


414430AI346201Hs.76118ubiquitin carboxyl-terminal3.2
esterase Li


439924AI985897Hs.125293ESTs 3.2


411505AF155659Hs.70565molybdenum cofactor 3.2
synthesis 2


423175W27595Hs.18653hypothetical protein 3.2
FLJ14627


415115AA214228Hs.127751hypothefical protein 3.2


407878D87468Hs.40888activity-regulated 3.2
cytoskeleton-associat


410274AA381807Hs.61762hypoxia-inducible protein3.2
2


437762178028Hs.154679synaptotagmin I 3.2


4$8944AA302517Hs.92732KIAA1444 protein 3.2


6~ 450313A1038989Hs.332633Bardet-Biedlsyndroine 3.2
2


409459D86407Hs.54481low density lipoprotein3.2
receptor-related


410953AW811766Hs.334858hypothetical protein 3.2
MGC12250


418527AA450386Hs.7149Homo Sapiens cDNA: 3.2
FLJ21950 fis, clone
H


420061AW510776Hs.94958tubulin tyrosine ligase-like3.2
1


429496AA453800Hs.192793ESTs 3.2


430099AW194988Hs.20537hypothefical protein 3.2
FLJ13942


434928AW015595Hs.4267Homo Sapiens clones 3.2
24714 and 24715 mRNA


435532AW291488Hs.117305Homo Sapiens, clone 3.2
IMAGE:3682908, mRNA


438306AW188266Hs.163645ESTs 3.2


439274AF086092Hs.48372ESTs 3.2


440847AA907511Hs.130178ESTs 3.2


447750A1422234Hs.143434contactin 1 3.2


455350AW901809 gb:OVO-NN1020-170400-195-h023.2
NN1020 Homo


430890X54232Hs.2699glypican 1 3.2


420568F09247Hs.247735protocadhedn alpha 3.2
10


410768AF038185Hs.66187Homo Sapiens clone 3.2
23700 mRNA sequence


427450AB014526Hs.178121KIAA0626 gene product 3.2


430456AA314998Hs.241503hypotheficalprotein 3.2


430181AF065314Hs.234785cyclic nucleotide gated3.2
channel alpha 3


418512AW498974Hs.89981diacylglycerol kinase,3.2
zeta (104kD)


419912AF249745Hs.6066Rho guanine nucleotide3.2
exchange factor (


450689AI369275Hs.243010Homo Sapiens cDNA FLJ144453.2
fis, clone HE


424899AL119387Hs.119062'ESTs 3.2


166


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WO 03/025138 PCT/US02/29560
436277888520Hs.120917ESTs 3.2


451455A1937227Hs.8821hepcidin anfimicrobial3.2
peptide


445078AI869975Hs.4775junctaphilin 3 3.2


447746AW015920Hs.16i359ESTs 3
2


435458F11872Hs.4892Homo Sapiens clone .
24841 mRNA sequence 3.2


427729A8033100Hs.300646KIAA protein (similar 3.2
to mouse paladin)


417417F05745Hs.89512ATPase, Ca++Uansporting,3.1
plasma membra


438810AW897846Hs.6421hypothetical protein 3.1
DKFZp761 N09121


439570T79925Hs.269165ESTs, Weakly similar 3.1
to ALUt HUMAN ALU
S


1~432527AW975028Hs.102754ESTs 3,1


416801X98834Hs.79971sat (Drosophila)-like 3.1
2


421988AW450481Hs.161333ESTs 3.1


426509M31166Hs.2050pentaxin-rotated gene,3.1
rapidly induced b


408786AA773187Hs.294027ESTs 3
1


1 433494AB029396Hs.3353beta-1,3-glucuronylUansferase.
1(glucur 3.1


412723AA648459Ns.335951hypothetical protein 3.1
AF301222


d18329AW247430Hs.84152cystathionine-betasynthase3.1


439456A1752409Hs.109314hypothetical protein 3.1
FLJ20980


428832AA578229Hs.324239ESTs, Moderately similar3
to ZN91 HUMAN Z 1


ZO452780BE171598Hs.13522ESTs, Weakly similar .
to 138022 hypothefi 3.1


438192AI859065Hs.337620Homo Sapiens AFG3L1 3.1
isoform 1 mRNA, part


424939AK000059Hs.153881Homo Sapiens NY-REN-623.1
anfigen mRNA, par


403053858624Hs.2186eukaryofic translation3.1
elongation factor


404299 3
~ 1


~J'407864AF069291Hs.40539chromosome 8 open reading.
frame 1 3.1


410181A1468210Hs.261285pleiotropic regulator 3.1
1 (PRLt, Arabidops


4188528E537037Hs.273294hypotheficalprotein 3.1
FLJ20069


449101AA205847Hs.23016G protein-coupled receptor3.1


453240A196956dHs.166254hypothetical protein 3.1
DKFZp5661133


30440486BE243513Hs.7212hypothetical protein 3.1
PP1044


408096BE250162Hs.83765dihydrofolate reductase3.1


439864AI720078Hs.291997ESTs, Weakly similar 3.1
to A47582 B-cell gr


414706AW340125Hs.76989KIAA0097 gene product 3.1


436315BE390513Hs.27935hypothetical protein 3.1
MGG4837


35426855AL117427Hs.172778Homo Sapiens mRNA; 3.1
cDNA DKFZp566P013
(fr


425683ABD378i3Hs.159200hypothetical protein 3.1
DKFZp762K222


410126BE169274Hs.169387KIAA0036 gene product 3.1


d35312AJ243396Hs.4865voltage-gated sodium 3.1
channelbeta-3 subu


425491AA883316Hs.255221ESTs 1
3


456273AF154B46Hs.1148zincfingerprotein .
3.1


412140AA219691Hs.73625RAB6 interacting, kinesin-like3.1
(rabkines


445255NM Hs.12477synaptosomal-associated3.1
014841 protein, 91 kDa


432154AI701523Hs.112577ESTs 3.f


453128AW026516Hs.31791acylphosphatase 2, 3
muscle type 1


45438458AW975186 gb:EST387294 MAGE rosequences,.
MAGN Homo 3.i


448616AF035621Hs.21611kinesin family member 3.0
3C


429281AA830856Hs.29808Homo sapiens cDNA: ~
FLJ21122 fis, clone 3.0
C


443906AA348031Hs.7913ESTs 3.0


417318AW953937Hs.12891ESTs 0
3


50452619AW298597Hs.61884Homo sapiens, clone .
IMAGE:4298026, mRNA, 3.0


444153AK001610Hs.10414hypothetical protein 3.0
FLJ10748


408790AW580227Hs.47860neurotrophic Tyrosine 3.0
kinase, receptor,


426327W03242Hs.44898Homo Sapiens clone 3.0
TCCCTA00151 mRNA sequ


451468AW503398Hs.293663ESTs, Moderately similar3.0
to 138022 hypot


422758AF152329Hs.284180protocadherin gamma 3.0
subfamily C, 3


421633AF121860Hs.106260sorting nexin 10 3.0


428361NM Hs.183858lranscriptional intermediary3.0
015905 factor 1


416932L34059Hs.89484cadherin 4, type 1, 3.0
R-cadherin (refinal)


416805F13271Hs.79981Human clone 23560 mRNA3.D
sequence


419518U79289Hs.90798Human clone 23695 mRNA3.0
sequence


422709AA315331Hs.153485ESTs 3.0


423135N67655Hs.26411ESTs 3.0


424901211933Hs.182505POU domain, class 3, 3.0
transcripfion facto


426617W58006Hs.266258endonuclease G-like 3.0
6S 1


427386AW836261Hs.337717ESTs 3.0


429859NNt,.,007050Hs.225952protein tyrosine phosphatase,3.0
receptor t


435071D60683Hs.35495ESTs 3.0


435092AL137310Hs.4749Homo Sapiens mRNA; 3.D
cDNA DKFZp761 E13121
(


436211AK001581Hs.334828hypotheficalprotein 3.0
FLJ10719; KIAA1794


436936AL134451Hs.197478ESTs 3.0


445855BE247129Hs.145569ESTs 3.0


452294A187i925Hs.117895ESTs,ModeratelysimilartoA47582B-cel3.0


433980AA137152Hs.286049phosphoserine aminotransferase3.0


430228AW950939Hs.6382ESTs, Highly similar 3.0
to T00391 hypothefi


75451026AA013218Hs.157492cer-d4 (mouse) homolog3.0


435232NM Hs.4854cyclin-dependent kinase3.0
001262 inhibitor 2C (p1


439566AF086387 gb:Homo Sapiens full 3.0
length insert cDNA


425782U66468Hs.159525cell growth regulatory3.0
with EF-hand doma


416586D44643Hs.14144secreted modular calcium-binding3.0
protein


416874H98752Hs.42568ESTs 3.0


410386W26187Hs.3327Homo sapiens cDNA: 3.0
FLJ22219 fis, clone
H


411411AA345241Hs.55950ESTs, Weakly similar 3,0
to KIAA1330 protein


424066299348Hs.11246iESTs, Weakly similar 3.0
to 138022 hypo(heti


167


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
404048 3.0


429163AA884766 gb:am20a10.s1 Soares 3.0
NFL_T-GBC_S1 Homos


454117BE410100Hs.40368adaptor-related protein3.0
complex 1, sigma


418196AI745649Hs.26549KIAA1708 protein 3.0


434131AI858275Hs.143659ESTs 3.0


441255806350Hs.171635ESTs 2.9


453900AW003582Hs.226414ESTs, Weakly similar 2.9
to ALU8_HUMAN ALU
S


453905NM Hs.36566LIM domain kinase 1 2.9
002314


416602NM Hs.79389net (chicken)-like 2.9
006159 2


1 431173AW971198Hs.294068ESTs 2.9
~


425599AW366745Hs.214140ESTs, Weakly similar 2.9
to ALU1 HUMAN ALU
S


436401A1087958Hs.29088ESTs 2.9


422960AW890487Hs.63984cadherin 13, H-cadherin2.9
(heart)


451558NM Hs.26630ATP-binding cassette, 2.9
001089 sub-family A (ABCs


15 412490AW803564Hs.288850Homo sapiens cDNA: 2.9
FLJ22528 fis, clone
H


433149BE257672Hs.42949hypothetical protein 2.9
HES6


434811AW971205Hs.114280ESTs 2.9


425897AA935315Hs.48965Homo Sapiens cDNA: 2.9
FLJ21693 fis, clone
C


452092BE245374Hs.27842hypothefical protein 2.9
FLJ11210


453496AA442103Hs.33084solute carrier family 2.9
2 (facilitated glu


411124AW196937Hs.53929ESTs, Weakly similar 2.9
to ALUB HUMAN !!1l


419227BE537383Hs.89739cholinergic receptor, 2.9
nicotinic, beta po


427651AW405731Hs.18498Homo Sapiens cDNA FLJ122772.9
fis, clone MA


441707842637Hs.21963hypothetical protein 2.9
DKFZp761B0514


25 435741AI240668Hs.113099ESTs 2.9


437273AL137451Hs.120873ESTs, Highly similar 2.9
to T46266 hypotheti


422939AW394055Hs.98427ESTs, Weakly similar 2.9
to 138022 hypothefi


439376AA883521Hs.222064ESTs 2.9


439935S75105Hs.301676glutamate receptor, 2.9
ionotropic, kainate


30 437267AW511443Hs.258110ESTs 2.9


453740AL120295Hs.311809ESTs, Moderately similar2.9
to PC4259 fern


400250 2.9


400992 2.9


408814N62499Hs.176227hypothetical protein 2.9
FLJ11155


3 411849AW964970Hs.18861ESTs, Moderately similar2.9
to KIAA1276 pro


414853U31116Hs.77501sarcoglycan, beta (43kD2.9
dystrophin-assoc


423751AW235633Hs.46525ESTs 2.9


42691DAA470023Hs.190089ESTs,ModeratelysimilartoALU12.9
HUMANA


450203AF097994Hs.301528L-kynureninelalpha-aminoadipate2.9
aminoUa


40 459311840192Hs.21527Human DNA sequence 2.9
from clone GSi-115M3


425304AA463844Hs.31339fibroblast growth factor2.9
11


428500AI815395Hs.184641fatty acid desaturase 2.9
2


421641AI638184Hs.106334Homo sapiens clone 2.9
23836 mRNA sequence


421141AW117261Hs.125914ESTs 2.9


45 407870AB032990Hs.40719hypothetical protein 2.9
KIAA1164


456723243902Hs.4748adenylate cyclase activafing2.9
polypeptide


436456AW292677Hs.248122G protein-coupled receptor2.9
24


421483NM Hs.104717hypothetical protein 2.9
003388 MGC11333


412190816180Hs.274461ESTs 2.9


SO 446131NM Hs.290phospholipase A2, group2.9
000929 V


441668A1611973Hs.127525ESTs 2.9


437387A1198874Hs.28847AD026 protein 2.9


423420AI571364Hs.128382Homo sapiens mRNA; 2.9
cDNA DKFZp76111224
(f


427958AA418000Hs.98280potassium intermediate/small2.9
conductance


55 429084AJ001443Hs.195614splicing factor 3b, 2.9
subunit 3,130kD


447067842098Hs.21964ESTs 2.9


430887N66801Hs.260287KIAA1B41 protein 2.9


441824AB007871Hs.7977KIAA0411 gene product 2.9


42 AA335635Hs.96917ESTs 2.9
4126


6O , W01556Hs.238797ESTs, Moderately similar2.9
408739 to 138022 hypot


447422BE618703Hs.98258orthopedic (Drosphila)2.9
homolog


435615Y15065Hs.4975potassium voltage-gated2,9
channel, KOT-lik


446997AA383439Hs.16758Seir-1 protein 2.9


433573AF234887Hs.57652cadherin, EGF tAG seven-pass2.9
G-type rece


65 408447AK002089Hs.45080Homo Sapiens cDNA FLJ 2.9
11227 fis, clone PL


419586A1088485Hs.144759ESTs, Weakly similar 2.8
to 138022 hypotheti


417022NM Hs.80905Ras associafion (RaIGDSIAF-6)2.8
014737 domain fam


408432AW195262 gb:xn67b05.x1 NCI-CGAP-CML12.8
Homo sapiens


420320AB002361Hs.96633KIAA0363 protein 2.8


7O 425241AA324624Hs.155247aldolase C, fructose-bisphosphate2.8


428670AA431682Hs.134832ESTs 2.8


424415NM Hs.146580enolase 2, (gamma, 2.8
001975 neuronal)


409185AW961601Hs.252406hypothetical protein 2.8
FLJ12296 similar to


411555AFi Hs.70669HMP19 protein 2.8
13537


75 426847S78723Hs.2986235-hydroxytryptamine 2.8
(serotonin) receptor


458809AW9725i2Hs.20985sin3-associated polypeptide,2.8
30kD


420071AB028985Hs.94806ATP-binding cassette, 2.8
sub-family A (ABCs


424572M19650Hs.1507412',3'-cyclic nucleotide2.8
3' phosphodieste


444670H58373Hs.332938hypothetical protein 2.8
MGC5370


411089AA456454Hs.183418cell division cycle 2.8
2-like 1 (PITSLRE
pr


416111AA033813Hs.79018chromatin assembly 2.8
factor 1, subunilA
(


440637AW900115Ns.7309Homo Sapiens clone 2.8
23741 mRNA sequence


408554AA836381Hs.315111-nuclear receptor co-repressor/HDAC32.8
comp


168


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
403056856624Hs.2186eukaryotic translation2.8
elongation factor


423449AI497900Hs.33067ESTs 2.8


424188AW954552Hs.142634zinc finger protein 2.8


429006AA443143Hs.50929hypothetical protein 2.8
FLJ13842


434981AW182577Hs.293077ESTs 2.8


437435AA249439Hs.27027hypotheticalprotein 2.8
DKFZp762H1311


442748A1016713Hs.135787ESTs 2.8


443312N52025Hs.46616ESTs 2.8


450940A1744943Hs.143209ESTs, Weakly similar 2.8
to 138022 hypotheti


1 452738AL133800Hs.7086hypothetical protein 2.8
~ MGC12435


409182AA064970Hs.118145ESTs 2.8


439793AA018825Hs.7934Kroppel-like factor 2.8
4 (gut)


432683AW995441Hs.10475ESTs 2.8


434269AK001991Hs.3781similar to marine leucine-rich2.8
repeat pr


15 429500X78565Hs.289114hexabrachion (tenascin2.8
C, cytotactin)


433290820077Hs.302185Homo Sapiens clone 2.8
23618 mRNA sequence


434276AF123659Hs.93605leucine zipper, putative2.8
tumor suppresso


435977AL138079Hs.5012brain-specific membrane-anchored2.8
protein


430294A1538226Hs.32976guanine nucleotide 2.8
binding protein 4


20 425168896366 gb:yq37d04.s1 Soaresfetalliverspleen2.8


428180AI129767Hs.182874guanine nucleotide 2.8
binding protein (G
pr


409348AI401535Hs.146090ESTs 2.8


409887AL137534Hs.56876Homo Sapiens mRNA; 2.8
cDNA DKFZp434H1419
(f


457211AW972565Hs.32399ESTs, Weakly similar 2.8
to S51797 vasodilat


430039BE253012Hs.153400ESTs, Weakly similar 2.8
to ALUt HUMAN ALU
S


417642BE302665Hs.105461hypotheticalprotein 2.8
FLJ20357


419169AW851980Hs.262346ESTs, Weakly similar 2.8
to 572482 hypotheti


434008AA740878Hs.112982ESTs 2.8


446776AW293417Hs.156455ESTs 2.8


408838A1669535Hs.40369ESTs 2.8


422565BE259035Hs.118400singed (Drosophila)-like2.8
(sea urohin fas


447397BE247676Hs.18442E-tenzyme 2.8


412530AA766268Hs.266273hypothetical protein 2.8
FLJ13346


424330AW073953Hs.333396Homo Sapiens cDNA FLJ135962.8
fis, clone PL


35 446377AW014022Hs.170953ESTs 2.8


458924BE242158Hs.24427DKFZP56601646 protein 2.8


447710AI420523Hs.328241ESTs 2.8


404049 2.8


416913AW934714 gb:RCi-DT0001-031299-011-all2.8
DT0001 Homo


40 426400M78361Hs.i69743Homo Sapiens clone 2.8
25121 neuronal olfact


413264W26456Hs.i34757hypothetical protein 2.8
FLJ20033


458997AW937420Hs.69662ESTs 2.7


422864AA318323 gb:EST20390 Retina 2.7
II Homo Sapiens cDNA


430526AF181862Hs.242407G protein-coupled receptor,2.7
family C, gr


452023A8032999Hs.27566KIAA1173 protein 2.7


432022AL162042Hs.272348Homo sapiens mRNA; 2.7
cDNA DKFZp761 L1212
(f


452438BE514230Hs.29595JM4 protein 2.7


435408H07897Hs.4302ESTs, Weakly similar 2.7
to T29299 hypotheG


418791AA935633Hs.194628ESTs 2.7


438821AA826425Hs.291829ESTs 2.7


423464NM Hs.128856CSR1 protein 2.7
016240


442091AW770493Hs.182874guanine nucleotide 2.7
binding protein (G
pr


442242AV647908Hs.90424Homo Sapiens cDNA: 2.7
FLJ23285 fis, clone
H


412436AA665089 gb:nu76d01.s1 NCI CGAP_AIv12.7
Homosapiens


432821BE170702Hs.279005solute carrier family 2.7
5 21 (organic anion


416404AA180138Hs.107924ESTs 2.7


441364AW450466Hs.126830ESTs, Weakly similar 2.7
to YD38 YEAST HYPOT


450202AW969756Hs.34145ESTs, Weakly similar 2.7
' to 849647 GTP-bindi


428304AA374532Hs.124673Homo Sapiens cDNA FLJ 2.7
11477 fis, clone HE


60 428722U76456Hs.190787tissue inhibitor of 2.7
metalloproteinase
4


449701AW952323Hs.129908KIAA0591 protein 2.7


420372AW960049Hs.293660Homo Sapiens, clone 2.7
IMAGE:3535476, mRNA,


410318AA084050Hs.269259ESTs, Weakly similar 2.7
to S23650 retroviro


414603858394Hs.25119ESTs, Weakly similar 2.7
to YEXO_YEAST HYPOT


65 416096H18577Hs.88974cytochrome 1r245, beta2.7
polypeptide (chro


420896AW149342Hs.24444Homo Sapiens cDNA: 2.7
FLJ22165 tis, clone
H


424856AA347746Hs.9521ESTs, Weakly similar 2.7
to ZN43_HUMAN ZINC


436304AA339622Hs.108887ESTs 2.7


441027A1911412Hs.126444ESTs 2.7


7~ 452545N31940Hs.14434ESTs, Weakly similar 2.7
to 138022 hypotheG


454201A8023191Hs.44131KIAA0974 protein 2.7


448560BE613183Hs.23213ESTs 2.7


426807AA385315Hs.156682ESTs 2.7


425825A1929508Hs.159590lymphocyte antigen 2.7
6 complex, locus H


75 440351AF030933Hs.7179RAD1 (S. pombe) homolog2.7


425390A1092634Hs.156114protein tyrosine phosphatase,non-recept2.7


427624AA406245Hs.24895ESTs 2.7


426413AA377823 gb:EST90805 Synovial 2.7
sarcoma Homo sapien


422491AA338548Hs.117546neuronatin 2.7


424560AA158727Hs.150555protein predicted by 2.7
clone 23733


432415T16971Hs.289014ESTs, Weakly similar 2.7
to A43932 mucin 2
p


414865AA157155Hs.274414hypotheticalprotein 2.7
FLJ14457


415827H17462Hs.23079ESTs 2.7


169


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
445568H00918Hs.2687d4KIAA1796 protein 2.7


433315896754Hs.239706GRB2-associated binding 2.7
protein 1


428862NM Hs.2316SRY (sex determining 2.7
000346 region Y)-box 9 (ca


447959AI452784Hs.270270ESTs, Weakly similar 2.7
to 2109260A B cell


426420BE383808Hs.322430NDRG family, member 4 2.7


436899AA764852Hs.291567ESTs 2.7


444100AA383343Hs.22116CDC14 (cell division 2.7
cycle 14, S. cerevi


426501AW043782Hs.293616ESTs 2.7


449092091641Hs.22985alpha2,8-sialyltransferase2.7


1 427311AB020672Hs.175411KIAA0865 protein 2.7
~


453313BE005771Hs.153746hypothetical protein 2.7
FLJ22490


404029 2.7


416289W26333Hs.337438ESTs 2.7


439108AW163034Hs.6467synaptogyrin 3 2.6
'


I 418746AI955289Hs.300759ribosomal protein L36 2.6
S


412046Y07847Hs.73088RAS-related on chromsome2.6
22


435040AI932350Hs.152825ESTs 2.6


453083087223Hs.31622contactin associated 2.6
protein 1


428167AA770021Hs.16332ESTs 2.6


20 420028A8014680Hs.8786carbohydrate (N-acetylglucosamine-6-0)2.6
s


443715AI583187Hs.9700cyclin E1 2.6


421247BE391727Hs.102910generalUanscdpGonfactorIIH,polype2.6


424687J05070Hs.15173Bmatrix metalloproteinase2.6
9 (gelatinase B


415056AB004662Hs.77867adenosine A1 receptor 2.6


25 451697AW449774Hs.296380POM (POM121 rat homology2.6
and ZP3 fusion


433701AW445023Hs.15155ESTs 2.6


457358AI479755Hs.129010ESTs 2.6


430347Ntv>_002039Hs.239706GRB2-associated binding 2.6
protein 1


418027AB037807Hs.83293hypotheticalprotein 2.6


440491835252Hs.24944ESTs, Weakly similar 2.6
to 2109260A B cell


425171AW732240Hs.16365ESTs 26


459335AW298545Hs.250726EST 2.6


425402A1215881Hs.24970ESTs, Weakly similar 2.6
to 834323 GTP-bindi


453169A8037815Hs.32156KIAA1394 protein 2.6


35 433647AA603367Hs.222294ESTs 2.6


450414AI907735Hs.21446KIAAi716 protein 2.6


446233A1282028Hs.25205ESTs 2.6


415446F08898Hs.66075ESTs 2.6


445873AA250970Hs.251946poly(A)-binding protein,2.6
cytoplasmic 1-I


413012D83777Hs.75137KIAA0193 gene product 2.6


428671BE297851Hs.189482zinc finger protein 179 2.6


427158AA935603Hs.i66231ESTs 2.6


408988AL119844Hs.49476Homo Sapiens clone TUAB 2.6
Cri-du-chat regi


459516A1049662Hs.246858EST 2.6


45 402693 2.6


408039AA131424Hs.50340ESTs 2.6


422896AW961489Hs.154116ESTs 2.6


423130AW897586Hs.21213ESTs 2.6


438796W67821Hs.109590genethonin 1 2.6


50 439871888518Hs.46736hypothetical protein 2.6
FLJ23476


440192AA872282Hs.190596ESTs 2.6


419708AK000753Hs.92374hypothetical protein 2.6


449436AA860329Hs.279307hypothetical protein 2.6
DKFZp43412117


436870AW204219Hs.155560calnexin 2.6


55 448424AW009892Hs.31924ESTs 2.6


401324 2.6


414136AP,812434Hs.119023SMC2 (structural maintenance2.6
of chromoso


433943AA992805Hs.44865lymphoid enhancer-binding2.6
factor 1


428001H97428Hs.219907ESTs, Moderately similar2.6
Lo Transforming


429139F09092Hs.66087ESTs 2.6


423073BE252922Hs.1231MAD (mothers against 2.6
t decapentaplegic, Dr
9


448966AW372914Hs.86149phosphoinosilol 3-phosphate-binding2.6
prot


444001A1095087Hs.152299ESTs, Moderately similar2.6
to S65657 alpha


412049N53437Hs.18268adenylate kinase 5 2.6


65 441783BE313412Hs.7961Homo Sapiens clone 250122.6
mRNA sequence


425287888249Hs.155524peanut (Drosophila)-like2.6
2


432149AW614326Hs.i ESTs, Weakly similar 2.6
57022to T34549 probable


452234AW084176Hs.223296ESTs, Weakly similar 2.6
to 138022 hypotheti


453478AF083898Hs.33021neuro-ontological ventral2.6
antigen 2


7~ 418962AA714835Hs.271863ESTs 2.6


418858AW961605Hs.21145hypothetical protein 2.6
RG083M05.2


443257AI334040Hs.11614HSPC065 protein 2.6


428748AW593206Hs.98785Ksp37 protein 2.6


444984H15474Hs.132898fatty acid desaturase 2.6
1


75 433404T32982Hs.102720ESTs ~ 2.6


434779AF153815Hs.50151potassium inwardly-rectifying2.6
channel, s


420582BE047878Hs.99093Homo Sapiens chromosome 2.6
19, cosmid 82837


452856AF034799Hs.30881protein tyrosine phosphatase,2.6
receptor t


436440AI471862Hs.196008Homo Sapiens cDNA FLJ117232.6
fis, clone HE


438527AI969251Hs.115325RAB7, member RAS oncogene2.6
family-like 1


433216AF217412Hs.47320neuroligin 3 2.6


435380AA679001Hs.i92221ESTs 2.6


428966AF059214Hs.194687cholestero125-hydroxylase2.6


170


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
439653AW021103Hs.6631hypothetical protein 2.6
FLJ20373


419304AI271326Hs.146101ESTs, Weakly similar 2.6
to T45070 protein
k


422991H10940Hs.48965Homo Sapiens cDNA: 2.6
FLJ21693 fis, clone
C


448548813209Hs.21413salute carrier family 2.6
12, (potassium-chl


435370AI964074Hs.225838ESTs 2.6


408875NM Hs.48604DKFZP434B168 protein 2.5
015434


457005AJ007421Hs.i72597sat (Drosophila)-like 2.5
3


430154AW583058Hs.234726serine (orcysteine) 2.5
proteinase inhibito


438549BE386801Hs.21858trinucieofide repeat 2.5
containing 3


1 427951AI826125Hs.43546ESTs 2.5
~


411800N39342Hs.103042microtubule-associated2.5
protein 1B


457683AI821877Hs.140002ESTs, Moderately similar2.5
to ALU7 HUMAN A


451422AB002336Hs.26395erythrocyte membrane 2.5
protein band 4.1-li


430713AA351647Hs.2642eukaryotic franslation2.5
elongafion factor


1 428826AL048842Hs.194019attracfin 2.5



428963AW382682Hs.258208Homo Sapiens, clone 2.5
MGC:15606, mRNA, com


428141D50402Hs.182611solute carrier family 2.5
11 (proton-coupled


429550AW293055Hs.119357ESTs 2.5


438662AA223599Hs.6351cleavage and polyadenylafion2.5
specific fa


20 435760AF231922Hs.213004chromosome 21 open 2.5
reading frame 62


427513AI476318Hs.192480ESTs 2.5


430061AB037817Hs.230188KIAA1396 protein 2.5


435923BE301930Hs.5010Homo Sapiens clone 2.5
24672 mRNA sequence


417123BE326521Hs.159450ESTs 2.5


25 439699AF086534Hs.187561ESTs, Moderately similar2.5
to ALU1 HUMAN A


412980AI815750Hs.20977hypothetical protein 2.5
MGC3129 similar to


427209H06509Hs.92423KIAA1566 protein 2.5


424327AA431707Hs.31209ESTs 2.5


436340842246Hs.21606ESTs 2.5


450650T65617Hs.101257hypothefical protein 2.5
MGC3295


439444AI277652Hs.54578ESTs, Weakly similar 2.5
to 138022 hypotheti


400777 2.5


439478AF049460Hs.6574deformed epidermal 2.5
autoregulatory factor


450407NM Hs.24969gamma-aminobutyric 2.5
000810 acid (GAGA) A recepto


35 450385AI631024Hs.2494Bsynuclein, alpha inleracGng2.5
protein (sy


432558897268Hs.177269ESTs 2.5


400860 2.5


410361BE391804Hs.62661guanylate binding protein2.5
1, interferon-


416063BE047699Hs.93454ESTs 2.5


40 414998NM Hs.77729oxidised low density 2.5
002543 lipoprotein (lectin


452823AB012124Hs.30696transcription factor-like2.5
5 (basic helix


417791AW965339Hs.111471ESTs 2.5


418079840058Hs.6911ESTs 2.5


408495W68796Hs.237731ESTs 2.5


45 442104L20971Hs.188phosphodiesterase 4B, 2.5
cAMP-specific (dun


437370AL359567Hs.161962Homo Sapiens mRNA; 2.5
cDNA DKFZp547D023
(fr


429803W81489Hs.223025RAB31, member RAS oncogene2.5
family


424959NM Hs.153937activated p21cdc42Hs 2.5
005781 kinase


427413BE547647Hs.177781hypothetical protein 2.5
MGC5618


408955BE315170Hs.8087NAG-5 protein 2.5


415261T40928Hs.8346ESTs 2.5


415716N59294Hs.179662nucleosome assembly 2.5
protein 1-like 1


417873BE266659Hs.293659Homo Sapiens, Similar 2.5
to RIKEN cDNA A430


418388872332Hs.29258Homo Sapiens cDNA FLJ113642.5
fis, clone HE


55 421002AF116030Hs.100932transcription factor 2.5
17


423244AL039379Hs.209602ESTs, Weakly similar 2.5
to ubiquitous TPR
m


423553AA405635Hs.96854ESTs, Weakly similar 2.5
to DYLX_HUMAN CYTOP


427961AW293165Hs.143134ESTs 2.5


428301AW628666Hs.98440ESTs, Weakly similar 2.5
to 138022 hypoihe6


0 428508BE252383Hs.184668SB8131 protein 2.5


428858AA436760 gb:zv67d11.r1 5oares 2.5
total-fetus Nb2HF8-


428943AW086180Hs.37636ESTs, Weakly similar 2.5
to KIAA1392 protein


432427AL037630Hs.6638Homo Sapiens cDNA FLJ 2.5
11602 fis, clone HE


435347AW014873Hs.116963ESTs 2.5


65 437949U78519Hs.41654ESTs, Weakly similar 2.5
to A46010 X-linked


438208AL041224Hs.65379ESTs 2.5


440286U29589Hs.7138cholinergic receptor, 2.5
muscarinic 3


441523AW514263Hs.301771ESTs, Weakly similar 2.5
to ALUF HUMAN !!!!


441805AA285136Hs.301914neuronal specific franscription2.5
factor D


7~ 442337AI371029Hs.129257ESTs, Weakly similar 2.5
to TC17_HUMAN TRANS


442789AW904361Hs.131191ESTs, Weakly similar 2.5
to ALU7_HUMAN ALU
S


445556AI910241Hs.128B7actin-related protein 2.5
3-beta


449066AI628357Hs.208037ESTs 2.5


459583A1907673 gb:IL-BT152-080399-0042.5
BT152 Homo sapien


,75


TABLEB:
8


Pkey:Unique
Eos
probeset
idenfifier
number


CAT
number:
Gene
cluster
number


Accession: n numbers
Genbank
accessio


o


Pkey CAT
Number
Accession


4084321058667AW195262827868 AW811262
1


4122251284108_1AW902042N77591


171


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
412436 129439 1 AA665089 AA135130 AA484059 AA102419 AW877765
416120 1571266_1 H46739 H51513 H19779
416871 1626761 1 H98716 N90792 N24283
416913 163001 1 AW934714 BE161007 BE162500 AW749902 AW749864 BE162498 BE161005
AAi 90449 AW513465 BE161006 BE162499
422864 222336 1 AA318323 H 11145 815289 AA451945 AA476690 AA436954 243802
F11753 T65491 D81821
422949 223184 1 AA319435 N56456 AA319377 AW961532 T48452 AA894424
422977 223410-1 AA631498 A1017191 AA491211 AA761823 AA714555 AA768099 AA808286
AI934069 AA570223 AA574389 AA582438 AI7453d6 AW964510 AA319642
AW853758 H56414
423756 231725 1 AA828125 AA834883 AA330555
1 ~ 425168 247552_1 896366 AL133929 AA351636 H78818 AA477084 228957 H80194
425517 252729 1 AF121179 BE162736 AA358827
426413 266650 1 AA377823 AW954494 A1022688
428002 285602-1 AA418703 AA418711 BE071915 BE071920 BE071912
428679 294049 1 AA431765 AA432015
1 S 428858 296453_1 AA436760 AW237453 BE327d96 N47347 N56967
429007 298301 1 D80642 AA443145 AL119015 AW904500
429163 300543 1 AA884766 AW974271 AA592975 AA447312
433532 368950 1 AW975367 AA598607 AA742735
436190 41555 1 AK001059 AA633055
437034 431713 1 AA742643 AA808575 AW976668
438458 457837_1 AW975186 AA807807 D29548
438993 467651 1 AA828995 AA834879 AI926361
439566 47387 1 AF086387 W77884 W72711
440322 491966 1 AA879430 BE070262 BE070493 BE070272 BE070484 BE070397 BE070395
BE070201 BE070198 BE070404 BE070270 BE070400
25 444584 611496 1 A1168422 D80113 T59074
447197 711623 1 836075 AI366546 836167
448451 764066 1 AW015994 839898 AW000978 A1598202 A1521706
450625 84032 1 AW970107 AA513951 AA010406
452453 918300 1 AI902519 AI902518 AI902516
454996 1248640 1 AW850180 AW850326
455350 1283853-1 AW901809 AW901787 AW901795 AW901792 AW901744 AW901753
AW901807 AW90i798
TABLE BC:
Pkey: Unique number corresponding to an Eos probeset
35 Ref: Sequence source. The 7 digit numbers in this column are Genbank
Identifier (GI) numbers. "Dunham, et al." refers to the publication entitled
"The DNA
sequence of human chromosome 22" Dunham, et al. (1999) Nature 402:489-495.
Strand: Indicates DNA strand from which exons were predicted.
Nt-position: Indicates nucleotide positions of predicted exons.
Pkey Ref Strand Nt-position
400777 8131663 Plus 70745-71121
400780 8131663 Minus 118372-118619
400859 9757499 Minus 91888-92018,98131-96294,99474-99570
400860 9757499 Minus 151830-152104,152649-152744
45 400992 8096828 Plus 140390-140822
401324 9863791 Plus 234057-234174
402408 9796239 Minus 110326-110491
402604 9909420 Plus 20393-20767
402605 9909420 Minus 47680-47973
402693 8569863 Minus 82366-82515
402855 9662953 Minus 59763-59909
404029 7671252 Plus 108716-111112
404048 3688074 Minus 54421-56808
404049 3688074 Minus 75765-78155
5 404283 2276311 Minus 99460-99564
404299 5738652 Minus 3826-4025
404541 8318559 Plus 103456-103664
404584 9857511 Plus 138651-139153
404593 9944086 Minus 74922-75788
404721 9856648 Minus 173763-174294
404819 4678240 Plus 16223-16319,16427-16513,16736-16859,16941-17075,17170-
17287,17389-17529,18261-18357,18443-18578
405238 7249119 Minus 51728-51836
405771 7018349 Plus 91191-91254,91510-91589
405819 4007557 Plus 2830-2967
65 406311 9211559 Minus 137114-139033
TABLE 9A:ABOUT 1202 GENES UP-REGULATED IN GLIOBLASTOMA COMPARED TO NORMAL
ADULT CENTRAL NERVOUS SYSTEM (CNS)
Table 9A lists about 1202 genes up-regulated in glioblastoma compared to
normal adult central nervous system (CNS). These were selected from 59680
probesets on the
7~ AffymetrixlEos Hu03 GeneChip array such that the ratio of"average"
glioblastoma to "average" normal adult CNS tissues was greater than or equal
to 2Ø The "average"
glioblastoma level was set to the 75th percentile amongst various glioblastoma
tumors. The "average" normal adult CNS tissue level was set to the 95th
percentile amongst various

non-malignant tissues. In order to remove gene-specific background levels of
non-specific hybridization, the 10th percentile value amongst various non-
malignant tissues was
subtracted from both the numerator and the denominator before the ratio was
evaluated.
Pkey: Unique Eos prabeset identifier number
75 ExAccn: Exemplar Accession number, Genbank accession number
UnigenelD: Unigene number
Unigene Title: Unigene gene title
R1: Ratio of 75th percentile tumor to 95th percentile normal adult nervous
system tissue
Pkey ExAccn UnigenelD UnigeneTitle Rt
452461 N78223 Hs.108106 transcription factor 20.1
436895 AF037335 Hs.5338 carbonic anhydrase XII 15.2
453941 U39817 Hs.36820 ~ Bloom syndrome 14.2
172


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
443247BE614387Hs.333893c-MyctargetJP01 12.4


428330L22524Hs.2256matrix metalloproteinase12.0
7 (matrilysin,


447342AI199268Hs.19322Homo Sapiens, Similar 11.7
to RIKEN cDNA 2010


422163AF027208Hs.112360prominin (mouse)-like 11.4
1


439451AF086270Hs.278554heterochromatin-like 11.2
protein 1


424800AL035588Hs.153203MyoD family inhibitor 10.2


416111AA033813Hs.79018chromatin assembly 10.0
factor 1, subunit
A (


444190AI878918Hs.10526cysteine and glycine-rich9.9
protein 2


412140AA219691Hs.73625RAB6 interacting, kinesin-like9.9
(rabkines


1 449340AW235786Hs.195359hypothetical protein 9.8
~ MGC10954


409731AA125985Hs.56145thymosin, beta, identified9.4
in neuroblast


439978BE139460Hs.124673Homo Sapiens cDNA FLJ114778.9
fis, clone HE


411411AA345241Hs.55950ESTs, Weakly similar 8.9
to KIAA1330 protein


456516BE172704Hs.222746KIAA1610 protein 8.2


1 420092AA814043Hs.88045ESTs 7.9



422631BE218919Hs.118793hypothetical protein 7.9
FLJ10688


453392U23752Hs.32964SRY (sex determining 7.9
region Y)-box 11


438527AI969251Hs.115325RAB7, member RAS oncogene7.9
family-like 1


427581NM Hs.179703KIAA0129 gene product 7.8
014788


418661NM Hs.1189E2F transcripfion factor7.8
001949 3


440684Ai253123Hs.127356ESTs, Highly similar 7.8
to S21424 nesfin [H


429643AA455889Hs.167279FYVE-finger-containing7.7
RabS effector pro


409638AW450420Hs.21335ESTs 7.5


444665BE613126Hs.47783B aggressive lymphoma 7.5
gene


25 456759BE259150Hs.127792delta (Drosophila)-like7.5
3


412777AI335773Hs.270123ESTs 7.4


436607AW661783Hs.211061ESTs 7.3


432058AW665996Hs.130729ESTs, Weakly similar 7.3
to ALU1 HUMAN ALU
S


417061AI675944Hs.188691Homo Sapiens cDNA FLJ120337.3
fis, clone HE


3 428976AL037824Hs.194695ras homolog gene family,7.2
0 member I


433244A8040943Hs.271285KIAA1510 protein 7.1


436726AA324975Hs.128993ESTs, Weakly similar 7.1
to T00079 hypotheti


408432AW195262 gb:xn67b05.x1 NCI CGAP-CMLt7.1
Homo Sapiens


434164AW207019Hs.148135sedne/threonine kinase7.0
33


35 445673AA250970Hs.251946poly(A)-binding protein,7.0
cyloplasmic 1-I


439726AW449893Hs.293707ESTs, Weakly similar 7.0
to 138598 zinc fang


432656NM Hs.3076MHC class II transacfivator6.8
000246


431117AF003522Hs.250500delta (Drosophila)-like6.8
1


453387AI990741Hs.252809ESTs 6.8


418821AA436002Hs.183161ESTs 6.6


437034AA742643 gb:ny91c01.s1 NCI-CGAP-GCB16.6
Homosapiens


411252AB018549Hs.69328MD-2 protein 6.5


424687J05070Hs.151738matrix metalloproteinase6.4
9 (gelatinase 8


452953AI932884Hs.271741ESTs, Weakly similar 6.3
to A46010 X-linked


45 433532AW975367 gb:EST387475 MAGE resequences,6.3
MAGN Homo


420311AW445044Hs.38207Human DNA sequence 6.3
from clone RP4-530115


418097845137Hs.21868ESTs 6.2


407304AA565832 gb:nj32b03.s1 NCI CGAP_AA16.2
Homo Sapiens


435256AF193766Hs.13872cylokine-like protein 6.1
C17


449446D60730Hs.57471ESTs 6.1


403790 6.0


425517AF121179 gb:AF121179 Homo Sapiens6.0
liver (Chang L-


420674NM Hs.1327butyrylcholinesterase 6.0
000055


435542AA687376Hs.269533ESTs 5.9


55 418216AA662240Hs.283099AF15q14 protein 5.8


439086AF085947 gb:Homo sapiens full 5.8
length insert cDNA


408037AW271720Hs.42233hypothefical protein 5.7
FLJ10300


412225AW902042 gb:OVO-NN1022-170400-193-c025.7
NN1022 Homo


436109AA922153Hs.132760hypothetical protein 5.7
MGC15729


435005U80743Hs.306094tdnucleotide repeat 5.7
containing 12


429149AW193360Hs.197962ESTs, Weakly similar 5.7
to 136022 hypothe6


418113AI272141Hs.83484SRY (sex determining 5.6
region Y)-box 4


405558 5.6


442432BE093589Hs.38178hypoiheficalprotein 5.6
FLJ23468


65 442547AA306997Hs.217484ESTs, Weakly similar 5.6
to ALU1 HUMAN ALU
S


413063AL035737Hs.75184chitinase &like 1 (cartilage5.5
glycoprote


420560AW207748Hs.59115ESTs 5.5


408096BE250162Hs.83765dihydrofolatereduclase5.5


443539A1076182Hs.134074ESTs, Moderately similar5.4
to ALU6 HUMAN A


7~ 426318AA375125Hs.147112Homo Sapiens cDNA: 5.4
FLJ22322 fis, clone
H


429115AA446728Hs.289020Homo Sapiens cDNA FLJ140985.3
fis, clone MA


453900AW003582Hs.226414ESTs, Weakly similar 5.3
to ALUB HUMAN ALU
S


444168AW379879 gb:RC1-HT025&081199-011-f015.3
HT0256 Homo


432789D26361Hs.3104KIAA0042 gene product 5.3


75 437036A1571514Hs.133022ESTs 5.2


421247BE391727Hs.102910general transcription 5.2
factor IIH, polyps


441523AW514263Hs.301771ESTs, Weakly similar 5.2
to ALUF-HUMAN !!!!


451106BE382701Hs.25960v-myc avian myelocytomatosis5.1
viral relat


457211AW972565Hs.32399ESTs, Weakly similar 5.1
to S51797 vasodilat


454157AW162906Hs.312481ESTs, Weakly similar 5.1
to S66668 hydrogen


423343AA324643Hs.246106ESTs 5.1


425292NIvL005824Hs.15554537 kDa leucine-rich 5.1
repeat (L88) protein


406679AA070786 gb:zm66b07.ri Siratagene5.1
neuroepithelium


173


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WO 03/025138 PCT/US02/29560
442671A1005668Hs.134779EST 5.1


433001AF217513Hs.279905clone H00310 PR00310p15.0


418819AA228776Hs.191721ESTs 5.0


432946060899Hs.279854mannosidase alpha, 4
class 2B, member 9
1


420730NM Hs.99890polymerase (DNA directed),.
002691 delta 1, cata 4.9


441217AI922183Hs.2132d6ESTs 4,g


453385AW296101Hs.252806ESTs 4,8


418203X54942Hs.83758CDC28 protein kinase 4.7
2


450813AI739625Hs.203376ESTs 4
7


1 444006BE395085Hs.10086type I transmembrane ,
~ protein Fnl4 4.7


412530AA766268Hs.266273hypotheGcalprotein 4.7
F1J13346


431070AW40816dHs.249184iranscdp6on factor 4.7
19 (8C1)


429786AL080232Hs.220696Homo sapiens mRNA; 4.7
cDNA DKFZp586A061
(fr


405771 4
6


1 457065AI476318Hs.192480ESTs .
4.6


436190AK001059 gb:Homo Sapiens cDNA 4.6
FLJ10197 fis, clone


400859 4.6


435267N23797Hs.110114ESTs 4.6


443454A1057494Hs.133421ESTs 4
5


452811AA937079Hs.118983hypotheticalprotein .
FLJ12150 4.5


437267AW5114d3Hs.256110ESTs 4.5


435020AW505076Hs.301855DiGeorge syndrome 4.5
critical region gene
8


454269AI961060Hs.129908KIAA0591 protein 4.5


422106D84239Hs.111732Fc fragment of IgG 4
binding protein 5


25 422765AW409701Hs.1578baculoviral IAP repeat-containing.
5 (sur 4.5


456534X91195Hs.100623phospholipase C,beta 4.5
3,neighborpseudo


423756AA828125 gb:od71a09.s1 NCI_CGAP_Ov24.5
Homo Sapiens


417308H60720Hs.81892KIAA0101 gene product4.5


422170A1791949Hs.112432anti-Mullerian hormone4
4


429500X78565Hs.289114hexabrachion(tenascin.
C,cytotactin) 4.4


406568AF088886Hs.11590cathepsin F 4,4


426812AF105365Hs.172613solute camer family 4.4
12 (potassiumichlo


402516
4.4


432865AI753709Hs.152484ESTs, Weakly similar 4.4
to 138022 hypotheti


35 413625AW451103Hs.71371ESTs 4.4


436098820597Hs.9739glycerol-3-phosphate 4.4
dehydrogenase 1 (so


418333W92113 gb:zh48e01.r1 Soares 4.4
fetal liver_spleen


416933BE561850Hs.80506small nuclear dbonucleoprotein4.d
polypept


438192AI859065Hs.337620Homo Sapiens AFG3L1 4
isoform 1 mRNA 3
part


4~ 457374AA493662 , .
gb:nhO5d12.s1 NCI_CGAP4.3
Thy1 Homo Sapiens


433159AB035898Hs.150587kinesin-like protein 4.3
2


444386BE065183 gb:RC1-BT0314-020200-012-c044.3
BT0314 Homo


453202AW065781Hs.26270hypothetical protein 4.3
FLJ 11588


441020W79283Hs.35962ESTs 3
4


45 414733BE514535Hs.77171minichromosome maintenance.
deficient (S. 4.3


407902ALi Hs.41181Homo Sapiens mRNA; d.3
17474 cDNA DKFZp727C191
(fr


405701
4.3


451659BE37976iHs.i4248ESTs 4.3


418845AA852985Hs.89232chromobox homolog 4
5 (Drosophila HP1 2
alph


433323AA805132Hs.30701ESTs .
d,2


439811AA135332Hs.71608ESTs 4,2


415406T26510 gb:AB282F8R Infant 4.2
brain, LLNL array
of


436282891913Hs.272104ESTs, Moderately similar4.1
to ALU1_HUMAN A


441269AW015206Hs.178784ESTs 1
4


55 418727AA227609Hs.94834ESTs .
4.1


433006BE242758Hs.190223ESTs, Moderately similar4.1
to T29285 hypot


436480AJ271643Hs.87469putative acid-sensing4.i
ion channel


430786AAd86144Hs.31293ESTs 4.1


445372N36417Hs.144928ESTs 4
1


6Q 410555092649Hs.6431a disintegdn and metalloproteinase.
1 doma 4.0


457465AW301344Hs.122908DNA replication factor4.0


422094AF129535Hs.272027F-box only protein 4.0
5


442029AW956698Hs.14456neuralprecursorcellexpressed,develop4.0


459321AW044477Hs.299538ESTs 4
0


65 421308AA687322Hs.192843leucine zipper protein.
FKSG14 4.0


420567AK000812Hs.98874similar to proline-rich4.0
protein 48


447004AW296968Hs.157539ESTs 4.0


448295AI381911Hs.334859KIAA1814 protein 3.g


439699AF086534Hs.187561ESTs, Moderately similar3
to ALU1 HUMAN A 9


440704M69241Hs.162insulin-like growth .
factor binding prote 3.9


453096AW294631Hs.11325ESTs 3,g


457026AA397620Hs.48692ESTs 3,g


404642
3.9


450375AA009647Hs.8850a disintegrin and 3.9
75 metalloproteinase
doma


430132AA204686Hs.234149hypothetical protein 3.9
FLJ20647


437718AI927288Hs.196779ESTs 3,g


438490AW593272Hs.301299ESTs 3,g


429919AA460692Hs.2789d5hypotheticalprotein 3.g
FLJ23024


413604851767 gb:yg73g11.r1 Soares 3.9
infant brain 1NIB
H


425599AW366745Hs.214140ESTs, Weakly similar 3.9
to ALUt HUMAN ALU
S


448796AA147829Hs.301431endothelial zinc finger3,9
protein induced


449300AI656959Hs.222165ESTs 3.8


452203X57522Hs.158164transporter 1, ATP-binding3.8
cassette, sub


174


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
425769072513Hs.159486Human RPL13-2 pseudogene3.8
mRNA, complete


404295 3.8


410361BE391804Hs.62661guanylate binding protein3.8
1, interferon-


428728NM Hs.191381hypothetical protein 3.8
016625


409142AL136877Hs.50758SMC4 (structural maintenance3.8
of chromoso


430172AA468591Hs.161889ESTs 3.8


447499AW262580Hs.147674protocadherin beta 3.8
16


405684
3.8


437236AW137817Hs.244353ESTs 3.7


418883BE387036Hs.1211acid phosphatase 5, 3.7
tarfrate resistant


444143AW747996Hs.160999ESTs, Moderately similar3.7
to A56194 throm


425529NM Hs.158282KIAA0040 gene product 3.7
014656


425502898895Hs.125823ESTs 3.7


419741007019Hs.93002ubiquilin carrier protein3.7
NN~ E2-C


402424. 3.7


429469M64590Hs.27 glycine dehydrogenase(decarboxylating;3.7


434072H70854Hs.283059Homo Sapiens PR01082 3.7
mRNA, complete cds


414872082010Hs.77513COX10 (yeast) homolog,3.7
cytochrome c oxid


426071AW138057Hs.163835ESTs 3.7


419078M93119Hs.89584insulinoma-associated 3.7
1


428037N47474Hs.89230potassium intermediatelsmall3.7
conductance


416547H62914Hs.268946ESTs, Weakly similar 3.7
to PC4259 femitin


436899AA764852Hs.291567ESTs 3.6


436722AW975977 gb:EST388086 MACE rosequences,3.6
MAGN Homo


440652AI216751Hs.143977ESTs 3.6


428450NM Hs.184339KIAA0175 gene product 3.6
014791


452103842764Hs.339654ESTs, Weakly similar 3.6
to 138022 hypotheti


409048H59990Hs.37699ESTs 3.6


439546AF088056 gb:Homo Sapiens full 3.6
length insert cDNA


443544A1076315Hs.16359ESTs 3.6


418478038945Hs.1174cyclin-dependent kinase3.6
inhibitor 2A (me


435889AI249107Hs.269901ESTs 3.6


420301AA767526Hs.22030paired box gene 5 (B-cell3.6
lineage specif


438078A1016377Hs.131693ESTs 3.6


3 408420NM Hs.44766retinitis pigmentosa 3.6
S 006915 2 (X-linked recessi


416871H98716 gb:yx13d08.s1 Soares 3.5
melanocyte 2NbHM Ho


424085002914Hs.139226replication factor 3.5
Ntu> C (activator 1) 2
(40


446291_. Hs.i4623interferon, gamma-inducible3.5
8E397753 protein 30


432281AK001239Hs.274263hypotheticalprotein 3.5
FLJ10377


436123AA057484Hs.35406ESTs, Highly similar 3.5
to unnamed protein


411256AW834039 gb:OVO-TT0010-091199-053-e093.5
TT0010 Homo


419239AA468183Hs.184598Homo Sapiens cDNA: 3.5
FLJ23241 fis, clone
C


435065BE064391 gb:RC4-8T0310-110300-015-b083.5
BT0310 Homo


435532AW291488Hs.117305Homo Sapiens, clone 3.5
IMAGE:3682908, mRNA


45 447101N72185Hs.44189ESTs 3.5


410530M25809Hs.64173ATPase, H+transporfing,3.5
lysosomal (vacu


422156N34524 gb:yy56d10.s1 Soares_multiple3.5
sclerosis_


453616003462Hs.33846dynein, axonemal, light3.5
NM intermediate pot


439743_ Hs.283858Homo Sapiens mRNA full3.5
AL389956 length insert cDN


453884AA355925Hs.36232KIAA0186 gene product 3.5


424954NM Hs.1846tumor protein p53 (Li-Fraumeni3.5
000546 syndrome)


420721AA927802Hs.159471ZAP3 protein 3.5


426764AA732524Hs.15146dESTs, Weakly similar 3.4
to ALUC HUMAN !Ill


420649AI866964Hs.124704ESTs, Moderately similar3.4
to S65657 alpha


5 448831AL080123Hs.22182zinc finger protein 3.4
5 23 (KOX 16)


444371BE540274Hs.239forkhead box M1 3.4


402604 3.4


442407AW469584Hs.32353mitogen-activated protein3.4
kinase kinase


41 AI304870Hs.188680 3.4
4300 ESTs


, H58373Hs.332938 3.4
444670 hypothetical
protein
MGC5370


414550BE379808 gb:601159567T1 NIH_MGC-533.4
Homo Sapiens c


452211AI985513Hs.233420 3.4
ESTs


414416AW409985Hs.76084hypothetical protein 3.4
MGC2721


449961AW265634Hs.133100 3.4
ESTs


65 413257BE075035 gb:PM3-BT0584-260300-002-g053.4
BT0584 Homo


453857AL080235Hs.35861DKFZP586E1621 protein 3.4


417404NM plecksUin homology-like3.4
007350 domain, iamily
Hs.82101


422846BE513934Hs.1583neutrophil cytosolic 3.4
factor 1 (47kD, chr


446189H85224Hs.21d013 3.4
ESTs


70 437385AA757055Hs.164060 3.4
ESTs


453652AW009640Hs.28368ESTs, Moderately similar3.4
to S65657 alpha


408298AI745325Hs.271923 3.4
Homo
Sapiens
cDNA:
FLJ22785
tis,
clone
K


455778BE088746 gb:CM2-BT0693-210300.123-d093.3
BT0693 Homo


417546H65569Hs.18845ESTs 3.3


75 412471M63193Hs.73946endothelial cell growth3.3
factor 1 (platel


454631AW811324 gb:IL3-ST0141-131099-017-A023.3
ST0141 Homo


454294AB000734Hs.50640 3.3
JAK
binding
protein


457131AC002310Hs.301463 3.3
Human
Chromosome
16
BAC
clone
CIT987SK-A


410102AW248508 3.3
Hs.279727
Homo
Sapiens
cDNA
FLJ14035
fis,
clone
HE


0 449676AW380579 3.3
Hs.209657
ESTs


436211AK001581Hs.334828 3.3
hypotheticalprotein
FLJ10719;
KIAA1794


453746 gb:DKFZp761H119-rt 3.3
AL120611 761 (synonym:hamy2)


452799 Hs.213786 3.3
A1948829 ESTs


175


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
435380AA679001Hs.192221ESTs 3.3


426746J03626Hs.2057uddine monophosphate 3.3
synthetase(orotat


453362H14988Hs.107375ESTs 3.3


456473A1202788Hs.25682Homo Sapiens mRNA for 3.3
KIAA1863 protein,


416426AA180256Hs.210473Homo Sapiens cDNA FLJ148723.3
tis, clone PL


445777AI580371Hs.145384ESTs 3.3


423757AL049337Hs.132571Homo Sapiens mRNA; 3.3
cDNA DKFZp564P016
(fr


431941AK000106Hs.272227Homo Sapiens cDNA FLJ200993.3
tis, clone CO


404299 3.3


1 404108 3.3
~


425189H16622 gb:ym26c07.r1 Soares 3.3
infant brain iNIB
N


449318AW236021Hs.78531Homo Sapiens, Similar 3.3
to RIKEN cDNA 5730


d50193AI916071Hs.15607Homo Sapiens Fanconi 3.2
anemia complementat


427725U66839Hs.180533mitogen-activated protein3.2
kinase kinase


15 424051AL110203Hs.138411Homo Sapiens mRNA; 3.2
cDNA DKFZp586J1922
(f


418968NM Hs.89538cholesteryl ester transfer3.2
000078 protein, plas


449248M33782Hs.23391Homo Sapiens, Similar 3.2
to transcription f


439416W58294Hs.56254ESTs 3.2


401596AA172106Hs.110950Rag C protein 3.2


408380AF123050Hs.44532diubiquitin 3.2


450325AI935962Hs.26289ESTs 3.2


428730AA625947Hs.25750ESTs 3.2


457536AA305233Hs.278712eukaryotic translation3.2
initiation factor


426836N41720Hs.172684vesicle-associated 3.2
membrane protein 8
(e


25 442710A1015631Hs.23210ESTs 3.2


435232NM-001262Hs.4854cyclin-dependent kinase3.2
inhibitor 2C (pi


430970A1018210Hs.144083ESTs 3.2


416192NM Hs.998peroxisome proliferative3.2
005036 activated recep


446676H09380Hs.3D0965ESTs 3.2


451459A1797515Hs.270560ESTs, Moderately similar3.2
to ALU7_HUMAN A


407603AW955705Hs.62604Homo Sapiens, clone 3.2
IMAGE:4299322, mRNA,


413840AI301558Hs.146381RNA binding motif protein,3.2
X chromosome


448751BE551203Hs.201792ESTs 3.2


432593AW301003Hs.51483ESTs, Weakly similar 3.2
to hypothetical pro


35 458786AI457098Hs.280848ESTs 3.2


455909BE156417Hs.278798ESTs 3.2


419311AA689591 gb:nv66a12.s1 NCI CGAP_GCB13.2
Homo Sapiens


439710AF086543 gb:Homo Sapiens full 3.2
length insert cDNA


434559AF147315 gb:Homo Sapiens full 3.1
length insert cDNA


40 455800822479Hs.167073Homo Sapiens cDNA FLJ130473.1
fis, clone NT


d36703AW880614Hs.146381RNA binding motif protein,3.1
X chromosome


414799AI752416Hs.77326insulin-like growth 3.1
factor binding prate


437860AA333063Hs.279898Homo Sapiens cDNA: 3.1
FLJ23165 fis, clone
L


434182W20309Hs.118520G-protein gamma-12 3.1
subunit


45 417900BE250127Hs.82906CDC20 (cell division 3.1
cycle 20, S. cerevi


434769AA648884Hs.134278Homo Sapiens cDNA FLJ126763.1
tis, clone NT


414825X06370Hs.77432epidermal growth factor3.1
receptor (avian


426413AA377823 gb:EST90805 Synovial 3.1
sarcoma Homo sapien


447959AI452784Hs.270270ESTs, Weakly similar 3.1
to 2109260A B cell


404589 3.1


421764AI681535Hs.148135serine/threonine kinase3.1
33


419986AI345455Hs.78915GA-binding protein 3.1
Uanscription factor,


416941BE000150Hs.48778niban protein 3.1


414761AU077228Hs.77256enhancer of zeste (Drosophila)3.1
homolog 2


55 449611AI970394Hs.197075ESTs 3.1


434746AA648368Hs.295368ESTs 3.1


434274AAti28539Hs.116252ESTs, Moderately similar3.1
to ALUt HUMAN A


427899AA829286Hs.332053serum amyloid A1 3.1


417642BE302665Hs.105461hypothetical protein 3.1
FLJ20357


452472AW957300Hs.294142ESTs, Weakly similar 3.1
to C55663 oligodend


446131NM Hs.290phospholipase A2, group3.1
000929 V


440052AI633744Hs.195648ESTs, Weakly similar 3.1
to 138022 hypotheti


426531AA381071 gb:EST94100 Activated 3.1
T-cells XII Homo s


422158L10343Hs.112341protease inhibitor 3.1
3, skin-derived (SKAL


65 aos2s7 3.1


447039AV661798Hs.2829i5ESTs 3.1


404802 3.1


406927M26460 gb:Homo Sapiens (clone3.1
104) retinoblasto


419314AW971924Hs.87280ESTs 3.0


435894A1076667Hs.188011ESTs 3.0


432140AK000404Hs.272688hypothetical protein 3.0
FLJ20397


443426AF098158Hs.9329chromosome 20 open 3.0
reading frame 1


425202AW962282Hs.152049ESTs, Weakly similar 3.0
to 138022 hypotheti


407047X65965 gb:H.sapiens SOD-2 3.0
gene for manganese
su


75 418241M26682Hs.1149LIM domain only 1 (rhombotin3.0
1)


446599297832Hs.15476differentially expressed3.0
in FDCP (mouse


412950BE018581Hs.245342hypotheticalprotein 3.0
FLJ14642


428670AA431682Hs.134832ESTs 3.0


446975BE246446Hs.i6695ubiquitin-activating 3.0
enzyme E1-like


437756AA767537Hs.197096ESTs 3.0


416084L16991Hs.79006deoxythymidylate kinase3.0
(thymidylate kin


402374AL135225Hs.301865dopachrome tautomerase3.0
(dopachrome delta


443885H91806Hs.15284ESTs 3.0


176


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
434008 Hs.112982 ESTs 3.0
AA740878


452568AA805634Hs.300870 Homo Sapiens mRNA;3.0
cDNA DKFZp547M072 (fr


414239AI288330Hs.182330 ESTs 3.0


421013M62397Hs.1345 mutated in colorectal3.0
cancers


424635AA420687Hs.115455 Homo Sapiens cDNA 3.0
FLJ14259 fis, clone PL


410276AI554545Hs.68301 ESTs 3.0


433865N29862Hs.44104 ESTs 3.0


406028 3.0


401626 3.0


1 415949H10562Hs.21691 ESTs 3.0
~


418583AA604379Hs.86211 hypothetical protein3.0


417933X02308Hs.82962 thymidylate synthetase3.0


434577837316Hs.179769 Homo Sapiens cDNA:3.0
FLJ22487 fis, clone H


430437AI768801Hs.169943 Homo Sapiens cDNA 3.0
FLJ13569 fis, clone PL


15 427940AA417812Hs.38775 ESTs 2~9


456060C14904Hs.45184 Homo Sapiens cDNA 2.9
FLJ12284 fis, clone MA


421988AW450481Hs.161333 ESTs 2.9


448775AB025237Hs.388 nudix (nucleoside 2.9
diphosphate linked mot


438598AI805943Hs.326067 hypotheficalprotein2~9
MGC5i78


429612AF062649Hs.252587 pituitary tumor-Uansforming2.9
1


451189AA016019Hs.d0905 ESTs 2~9


401558 2'9


426207BE390657Hs.30026 HSPC182 protein 2~9


404721 2'9


401384 2'9


417288AI984792Hs.108812 hypothetical protein2~9
FLJ22004


427648AI376722Hs.180062 proteasome (prosome,2.9
macropain) subunit,


435928H64345Hs.183961 ESTs 2~9


431740N75450Hs.183412 ESTs, Moderately 2.9
similar to AF116721 67


428242H55709Hs.2250 leukemia inhibitory 2.9
factor (cholinergic


439972AI348100Hs.124662 ESTs 2~9


433112AA973801Hs.144553 ESTs, Weakly similar2.9
to unnamed protein


423751AW235633Hs.46525 ESTs 2~9


406748AW339106Hs.217493 annexin A2 2~9


3 422154T79045Hs.126927 ESTs 2.9



405588 2'9


440911AA909536Hs.143562 ESTs 2~9


412420AL035668Hs.73853 bone morphogenetic 2~9
protein 2


445043AW014413Hs.196066 ESTs 2~9


410114AW590540Hs.271280 ESTs 2.9


419217AA504571gb:aa60e12.r1 NCI_CGAP GCBs 2.9
Homo Sapiens


415849820529Hs.6806 ESTs 2~9


448140AF146761Hs.20450 BCM-like membrane 2.9
protein precursor


453331AI240665Hs.8895 ESTs 2~9


45 432065AA401039Hs.2903 protein phosphatase 2.9
4 (formerly X), cata


438380T06430Hs.6194 chondroitin sulfate 2.9
proteoglycan BEHABIb


454377AA076811gb:7B03C12 Chromosome 7 Fetal2.9
Brain cDNA


421491H99999Hs.42736 ESTs 2~9


452291AF015592Hs.28853 CDC7 (cell division2.8
cycle 7, S. cerevisi


415446F08898Hs.66075 ESTs 2.8


439518W76326gb:zd60d04.r1 Soares fetal_heart_NbHH19W2.8


427221L15409Hs.174007 von Hippel-Lindau 2.8
syndrome


422493AW474183Hs.250173 hypothetical protein2.8
FLJ13158


419451AI907117Hs.90535 syntaxin binding 2.8
protein 2


55 448789BE539108Hs.22051 hypothetical protein2.8
MGC15548


424126AA335635Hs.96917 ESTs 2.8


458695AV660159Hs.282284 ESTs, Weakly similar2.8
to 138022 hypotheti


418973AA233056Hs.191518 ESTs 2.8


440471AA886146Hs.307944 ESTs 2.8


()~421016AA504583Hs.101047 transcription factor2.8
3 (E2A immunoglobul


433647AA603367Hs.222294 ESTs 2.8


415817U88967Hs.78867 protein tyrosine 2.8
phosphatase, receptor-t


421723AA620400Hs.300717 sodium channel, 2.8
voltage-gated, type III,


434964AI638850Hs.130746 ESTs 2.8


432022AL162042Hs.272348 Homo Sapiens mRNA;2.8
cDNA DKFZp761L1212 (f


400517AF242388Hs.149585 lengsin 2.8


433023AW864793Hs.87409 thrombospondin 1 2.8


448734BE614070Hs.326416 Homo sapiens mRNA;2.8
cDNA DKFZp564H1916 (f


406736AI254733Hs.182426 ribosomal protein 2.8
S2


409207AW373564Hs.194637 BANP homolog, SMAR12.8
homolog


440196N72847Hs.125221 ESTs 2.8


403961 2.8


425193AW965689Hs.22509 ESTs 2.8


425268A1807883Hs.180059 Homo Sapiens cDNA 2.8
FLJ20653 fis, clone KA


75 440483AI200836Hs.150386 ESTs 2.8


412391AW947710gb:RCO-MT0004-130300-011-e072.8
MT0004 Homo


448769N66037Hs.38173 ESTs 2.8


411632AW854829gb:OV2-CT0261-201099-011-f012.8
CT0261 Homo


438221AI798853Hs.122224 ESTs, Weakly similar2.8
to ALU5_HUMAN ALU S


457578AA578027gb:n120hOt.s1 NCI CGAP HSCi 2.8
Homo Sapiens


455510AA422029Hs.143640 ESTs, Weakly similar2.8
to hyperpclanzatio


447769AW873704Hs.320831 Homo Sapiens cDNA 2.8
FLJ14597 fis, clone NT


427701AA411101Hs.243886 nuclear autoantigenic2.8
sperm protein (his


177


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
433800A1034361Hs.135150lung type-I cell membrane-associated2.8
gly


439662H97552Hs.269060ESTs 2.8


425694U51333Hs.159237hexokinase 3 (white 2.8
cell)


414747U30872Hs.77204centromere protein 2.8
F (3501400kD, mitosin


414598A1094221Hs.135150lung type-t cell membrane-associated2.8
gly


447752M73700Hs.105938lactotransfertin 2.8


408761AA057264Hs.238936ESTs, Weakly similar 2.8
to (detline not ava


453350AI917771Hs.61790hypothetical protein 2~7
FLJ23338


456629AW891965Hs.279789histone deacetylase 2~7
3


1 439538AA837323Hs.164047ESTs 2.7
~


458814A1498957Hs.170861ESTs, Weakly similar 2.7
to 2195-HUMAN ZINC


456029BE255990Hs.218329hypothetical protein 2~7


451129BE072881 gb:RC2-BT0548-200300-012-e092.7
BT0548 Homo


456412AW749617Hs.280776tankyrase, TRF1-interacting2.7
ankyrin-vela


1 453536AA137000Hs.62578ESTs 2.7
S


438378AW974529Hs.86434hypothetical protein 2~7
FLJ21816


425745U44060Hs.14427Homo Sapiens cDNA: 2.7
FLJ21800 fts, clone
H


446322N23033Hs.15581dESTs 2.7


451592A1805416Hs.213897ESTs ~7


429466M85835Hs.12827ESTs 2.7


429747M87507Hs.2490caspase 1, apoptosis-related2.7
cysteine pr


455514AW983871 gb:RC1-HN0003-220300-021-h072.7
HN0003 Homo


414732AW410976Hs.77152minichromosome maintenance2.7
deficient (S.


444207AI565004Hs.79572cathepsin D (lysosomal2.7
aspartyl protease


427421AA402414Hs.3059coatomer protein complex,2.7
subunit beta


449655A1021987Hs.59970ESTs 2.7


422648D86983Hs.118893Melanoma associated 2.7
gene


428494AA233439Hs.184634hypothetical protein 2.7
FLJ20005


406895X60648Hs.172550polypyrimidine tract 2.7
binding protein (he


453255AA278167Hs.19215Homo Sapiens, clone 2.7
IMAGE:3605822, mRNA


427348NM Hs.177258PR00650 protein 2.7
014137


435370AI964074Hs.225838ESTs 2.7


407862BE548267Hs.50724Homo Sapiens cDNA 2.7
FLJ10934 fis, clone
OV


411874AA096106Hs.20403ESTs 2.7


421192AA833718Hs.204529KtAA1806 protein 2~7


435899W89093Hs.189914ESTs 2.7


414603858394Hs.25119ESTs, Weakly similar 2.7
to YEXO-YEAST HYPOT


453462AL037291Hs.236605ESTs, Moderately similar2.7
to ALU4-HUMAN A


436554AI985810Hs.301173ESTs 2.7


427528AU077143Hs.179565minichromosome maintenance2.7
deficient (S.


403881 2.7


431779AW971178Hs.268571apolipoprotein GI 2.7


404984


448275BE514434Hs.20830kinesin-like 2 2.7


45 446839BE091926Hs.16244mitotic spindle coiled-coif2.7
related prot


411927BE274009Hs.772glycogen synthase 2.7
1 (muscle)


404756 2.7


447072D61594Hs.17279iyrosylprotein sulfotransferase2.7
1


422176H80977 gb:yu89a11.s1 Soares 2.7
fetal liver spleen


439627BE621702Hs,29076hypothetical protein 2.7
FLJ21841


436532AA721522 gb:nv54h12.r1 NCI 2.7
CGAP_Ew1 Homosapiens


412833AW960547Hs.298262ribosomal protein 2.7
S19


457245AI745498Hs.204579ESTs 2.7


446861A1696519Hs.14427Homo Sapiens cDNA: 2.7
FLJ21800 fis, clone
H


55 453263891778Hs.99369ESTs 2.7


459385BE380047 gb:601159362F2 NIH_MGC-532.7
Homo Sapiens c


438764AA824524Hs.336452ESTs 2.7


429285AI971081Hs.20432ESTs, Weakly similar 2.7
to 138022 hypotheli


424853BE549737Hs.132967Human EST clone 1228872.7
mariner transposo


60 430037BE409649Hs.227789mitogen-activated 2.7
protein kinase-activat


449892N73608Hs.50309ESTs 2.7


454201AB023191Hs.d4131KIAA0974 protein 2.7


452279AA286844Hs.61260hypothetical protein 2.7
FLJ 13164


427954J03060Hs.247551metaxin 1 2.7


65 400371U80740 2.7


452449AW068658Hs.209d3ESTs 2.7


431114AA492400Hs.291015ESTs 2,7


417088M54915Hs.81170pim-1 oncogene 2.7


447674BE270640Hs.19192cyctin-dependent kinase2.7
2


70 403680 2.7


454679AW813110 gb:CM4-ST0189-051099-021-fi052.7
ST0189 Homo


411968AI207410Hs.69280Homo Sapiens, clone 2.6
IMAGE:3636299, mRNA,


422240860594Hs.29002KIAA1706 protein 2.6


424368AB037766Hs.146085 2.6
KIAA1345
protein


405808 2.6


419700AF084935Hs.92357galactokinase 1 2.6


435972W95088Hs.114198 2~6
ESTs


453568S70782Hs.557adrenergic, alpha-1D-,2.6
roceptor


443725AW245680Hs.9701growth arrest and 2.6
DNA-damage-inducible,


444156AW500059Hs.86437ESTs, Highly similar 2.6
to AF2191401 gastr


428209AA424197Hs.98947ESTs, Weakly similar 2.6
to S33496 trypsin
[


437640AA76d893Hs.272155 2.6
ESTs,
Weakly
similar
to
138022
hypothe6


453948AI970797Hs.64859ESTs 2.6


17$


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
415402AA164687Hs.177576mannosyl (alpha-1,3-)-glycoprotein2.6
beta-


425397J04088Hs.156346topoisomerase (DNA) 26
II alpha (170kD)


418228AA962181Hs.111219ESTs,ModeratelysimilartoALU12.6
I1UMANA


401324 2.6


425234AW152225Hs.165909ESTs, Weakly similar 2-6
to 138022 hypotheti


443210AI692649Hs.9451hypothetical protein 2.6
MGC13168


457244AA581385Hs.162473ESTs, Weakly similar 2.6
to 138022 hypolheti


417144AA382104Hs.8i337lectin, galactoside-binding,2.6
soluble, 9


433933AI754389Hs.133494Homo Sapiens clone 2.6
TCCCIA00164 mRNA sequ


1 437437AA226869Hs.16520hypothetical protein 2.6
~ DKFZp762L0311


434206AW136973Hs.288516ESTs, Weakly similar 26
to S89890 mitogen
t


400992 2.6


455530AW984744 gb:RC1-HN0015-040400-011-d032.6
HN0015 Homo


436139AA765786Hs.120936ESTs 2.6


1 448330AL036449Hs.207163ESTs 2.6



412942AL120344Hs.75074mitogen-activated protein2.6
kinase-activat


432753NM Hs.336938Homo Sapiens PR00593 2.6
014075 mRNA, complete cds


433430AI863735Hs.186755ESTs 2.6


-036693AW973223Hs.303197B-cell CLLIIymphoma 2.6
7C


429482AF076974Hs.203952transformationltranscription2.6
domain-also


432715AA247152Hs.200483ESTs, Weakly similar 2.6
to KIAA1074 protein


414217AI309298Hs.279898Homo Sapiens cDNA: 2.6
FLJ23165 tis, clone
L


434165AA971328Hs.95361myosin VIIA (Usher 2.6
syndrome 18 (autosoma


414835AA156720Hs.185342ESTs 2.6


25 424489T48851Hs.149250D-siglec precursor, 2.6


436496AA281959Hs.5210glia maturation factor,2.6
gamma


403797 2.6


434573AW372340Hs.159717ESTs 2.6


418841NM Hs.89137low density lipoprotein-related2.6
002332 protein


415785882419Hs.23603ESTs, Moderately similar2.6
to ALUB-HUMAN A


450608AA010365Hs.193229ESTs 2.6


425304AA463844Hs.31339tibroblast growth factor2.6
11


432268BE311856Hs.2742303'-phosphoadenosine 2.6
5'-phosphosulfate
sy


d10507AA355288Hs.40834transitional epithelia2.6
response protein


35 d27343Ai880044Hs.176977protein kinase C binding2.6
protein 2


420917AW135716Hs.117330ESTs 2.6


414399L47345Hs.155202transcription elongation2.6
factor B (SIII)


446089AI860021Hs.270651ESTs, Moderately similar2.6
to A47582 B-cel


440829AF136407Hs.7446chromosome 6 open reading2.6
frame 5


406475AA315514Hs.47986hypothetical protein 2.6
MGC10940


450946AA374569Hs.i ESTs, Moderately similar2.6
27698to 2109260A B c


421462AF016495Hs.104624aquaporin 9 2.6


434846AW295389Hs.119768ESTs 2.6


422887AI751848Hs.492i5ESTs 2.6


45 417435NM Hs.82129carbonic anhydrase 2.6
005181 III, muscle specific


437389AL359587Hs.271586hypothetical protein 2.5
DKFZp762M115


408981AW500797Hs.49427Gem-interacting protein2.5


432180Y18418Hs.272822RuvB (E colt homology-like2.5
1


418079840058Hs.6911ESTs 2.5


437820AA769062Hs.323836ESTs, Weakly similar 2.5
to alternatively sp


439685AW956781Hs.293937ESTs, Weakly similar 2.5
to FXD2_HUMAN FORKH


425681AB018297Hs.i59183KIAA0754 protein 2.5


435177A1018174Hs.42936ESTs 2.5


437323AA371145Hs.226627leptin receptor 2.5


55 422114AW194851Hs.111801arsenate resistance 2.5
protein ARS2


448478A1523218Hs.203456ESTs 2.5


426623AA382826Hs.132793ESTs 2.5


448764A1568607Hs.182112ESTs 2.5


458385A1051489Hs.246214ESTs 2.5


403726N28939Hs.13434Homo Sapiens clone 2.5
24418 mRNA sequence


444888AI651039Hs.148559ESTs 2.5


456179H75490Hs.271930ESTs 2.5


424840D79987Hs.153479extra spindle poles, 2.5
S. cerevisiae, homo


406273NM Hs.83920peptidylglycine alpha-amidating2.5
000919 monooxyg


65 418054NM Hs.83354lysyl oxidase-like 2.5
002318 2


445936BE543594Hs.61478hypothetical protein 2.5
FLJ22329


454967AW848276 gb:IL3-CT0214-150200.074-E062.5
CT0214 Homo


442303AA989289Hs.129169ESTs 2.5


456583AF179897Hs.104105Meis (mouse) homolog 2.5
2


7~ 434263N34895Hs.44648ESTs 2.5


416692L24498Hs.80409growth arrest and DNA-damage-inducible,2.5


424528AW073971Hs.238954ESTs, Weakly similar 2.5
to KIAA1204 protein


406038Y14443Hs.88219zinc finger protein 2.5
200


413495Y12395Hs.315177interferon-related 2.5
developmental regulat


5 423098AA321980Hs.204682ESTs 2.5


410817A1262789Hs.93659protein disulfide isomerase2.5
related prot


439841AF038961Hs.6710mannose-P-dolichol 2.5
utilization defect
1


453828AW970960Hs.293B21ESTs 25


445034AW293376Hs.143659ESTs 2.5


o ~ BE407797Hs.23794checkpoint with forkhead2.5
449620 and ring finger


406876AI382286Hs.180842ribosomal protein L13 2.5


412370AW946614 gb:RC2-ET0021-280400-011-c052.5
ET0021 Homo


423642AW452650Hs.157148hypothetical protein 2.5
MGC13204


179


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
430357AW976789Hs.165607ESTs 2.5


414853U31116Hs.77501sarcoglycan, beta (43k02.5
dystrophin-assoc


416097BE387371Hs.i hypothetical protein 2.5
18964FLJ20085


428619AK002140Hs.187378hypothetical protein 2.5
FLJ11278


413976BE295452Hs.75655procollagen-proline, 2.5
2-oxoglutarate 4-di


445223AW291553Hs.254983ESTs 2.5


423926X03833Hs.1722intedeukin 1, alpha 2.5


410165BE560228Hs.71869apoptosis-associated 2.5
speck-like protein


406474 2.5


1 433908AW298141Hs.157975ESTs 2.5
~


439755AW748482Hs.77873B7 homolog 3 2.5


437528N59646Hs.169745crumbs (Drosophila) 2.5
homolog 1


420734AW972872Hs.293736ESTs 2.5


415346243108 gb:HSC13E071 normalized2.5
infant brain cDN


I 419337AW291112Hs.209978ESTs 2.5
S


444606809478Hs.18041ESTs 2.5


430061A8037817Hs.230188KIAA1396 protein 2.5


413407AI356293Hs.75339inositol polyphosphate2.5
phosphatase-like


411965BE467339Hs.280115ESTs 2.5


409278AA346683Hs.52763anaphase-promoting 2.5
complex subunit 7


403142 2.5


401714 2.5


425081X74794Hs.154443minichromosome maintenance2.5
deficient (S.


416505H66470Hs.16004ESTs 2.5


431518AA743462Hs.165337ESTs 2.5


448623BE613468Hs.107515ESTs, Weakly similar 2.5
to T00329 hypothe6


428301AW628666Hs.98440ESTs, Weakly similar 2.5
to 138022 hypotheti


404366 2.5


449733874546Hs.29438Homo Sapiens cDNA FLJ120942.5
fis, clone HE


459583AI907673 gb:IL-BT152-080399-0042.5
BT152 Homo sapien


402856AW939659 gb:RCO-DT0076-110100-031-c092.5
DT0076 Homo


420751J03019Hs.99913adrenergic, beta-1-, 2.4
receptor ~


d36805AA731533Hs.270751ESTs 2.4


420285AA256124Hs.293878ESTs, Moderately similar2.4
to ZN91 HUMAN Z


35 453496AA442103Hs.33084solute carrier family 2.4
2 (facilitated glu


453853AL040600Hs.188083ESTs 2.4


407909AW103986 gb:xd63e06.x1 NCI CGAP_Ov232.d
Homo Sapiens


454630BE142075 gb:CM3-HT0137-170999-012-f022.4
HT0137 Homc


451026AA013218Hs.157492cer-d4 (mouse) homolog2,4


420779L12398Hs.99922dopaminereceptor D4 2.4


438322AA804170Hs.221349ESTs 2.4


455908BE156306 gb:OVO-HT0367-150200-114-h042.4
HT0367 Homo


419625U91616Hs.91640nuclear factor of kappa2.4
light polypeptid


440773AA352702Hs.332541Homo Sapiens, Similar 2.4
to RIKEN cDNA 2700


45 450823T81223Hs.22011complement-c1q tumor 2.4
necrosis Factor-rel


447247AW369351Hs.287955Homo Sapiens cDNA FLJ130902.4
fis, clone NT


429109AL008637Hs.196352neutrophil cytosolic 2.4
factor 4 (40k0)


451802AI817711Hs.209374ESTs 2.4


419417892491Hs.39429ESTs 2.4


407094AF000574Hs.22405leukocyte immunoglobulin-like2.4
receptor,


423567BE252949Hs.69331hypothetical protein 2.4
FLJ13633


427501AI369280Hs.131743ESTs 2.4


451773242044Hs.26996KIAA1278 protein 2.4


436845AA732297Hs.113928ESTs 2.4


431584AW296121Hs.266263Homo Sapiens cDNA FLJ 2.4
5 14115 fis, clone MA


440614AA781530Hs.127236hypothetical protein 2.4
FLJ12879


423721AF176911Hs.132004cardiotrophin-like 2.4
cytokine; neurotrophi


452125BE312642Hs.28077GDP-mannose pyrophosphorylase2.4
B


41508AW997938Hs.90786ATP-binding cassette, 2.4
sub-family C (CFTR


453446BE299996 gb:600944574F1 NIH_MGC-172.4
Homo Sapiens c


419792AA250890Hs.190037ESTs 2.4


452786861362Hs.106642ESTs, Weakly similar 2.4
to T09052 hypotheti


410447AW816134 gb:MR3-ST0220-290100-016-e042.4
5T0220 Homo


438662AA223599Hs.6351cleavage and polyadenylation2.4
specific fa


65 402408 2.4


443950NM Hs.9999epithelial membrane 2.4
001425 protein 3


414625AA335738Hs.76686glutathione peroxidase2.4
1


403048 2.4


432088AA525454 gb:ni85c09.s1 NCI CGAP_Pr202.4
Homo Sapiens


70 431692AL021331Hs.267749unc93 (C.elegans) homolog2.4
A


455023AW850907 gb:IL3-CT0220-310100-065-H112.4
CT0220 Homo


426249F05422Hs.i68352nucleoporin-like protein2.4
1


446795AI797713Hs.156471ESTs 2.4


414774X02419Hs.77274plasminogen activator,2.4
urokinase


75 414252AA346483Hs.126191ESTs 2.4


417918AA209205Hs.i63754hypothetical proteinFLJ126062.4


427550BE242818Hs.179606nuclear RNA helicase, 2.4
DECD variant of DE


404020 2.4


407846AA426202Hs.40403CbpIp300-interacting 2.4
transactivator, wit


417222AI525424Hs.42053hypothetical protein ,
MGC23B3 . 2.4


443639BE269042Hs.9661proteasome (prosome, 2.4
macropain) subunit,


452706AW449390Hs.257150ESTs, Moderately similar2.4
to SUR1 HUMAN S


401676 2,4


Ig~


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
428882AA436915Hs.131748ESTs, Moderately similar2.4
to ALU7_HUMAN A


436277888520Hs.120917ESTs ~ 2.4


426271AF026547Hs.169047chondroitin sulfate 2.4
proteoglycan 3 (neur


405353 2.4


409193AA131483 gb:zo08e05.r1 Stratagene2.4
neuroepithelium


431431AL096711Hs.252953Human DNA sequence 2.4
from clone RP3-403A15


407889834556Hs.30800ESTs, Weakly similar 2.4
to S65657 alpha-1
G


453335AW857376Hs.169238fucosyltransferase 2.4
3 (galactoside 3(4)-L


450621AW297288Hs.55918hypothetical protein 2.4
FLJ11354


419652AL157485Hs.91973hypothetical protein 2.d


421151BE174431Hs.63386ESTs 2.4


437846AA773866Hs.244569esophagus cancer-related2.4
gene-2


420681AA847602Hs.106510ESTs, Moderately similar2.4
to ALU2-HUMAN A


405288 2.4


1 453527849570Hs.180236ESTs ' 2.4
5


429875A1091815 gb:qa58b06.s1 Scares-NhHMPu_Si2.4
Homosapi


436360AI962796Hs.136754ESTs 2.4


418592X99226Hs.284153Fanconi anemia, complementation2.4
group A


419991AJ000098Hs.94210eyes absent (Drosophila)2.4
homolog 1


449539W80363Hs.58446ESTs 2.4


419870AW403911Hs.266175phosphoprotein associated2.4
with GEMS


404584 2,4


454276AW294996Hs.255374ESTs 2.4


423746AW361817Hs.132370NADPH oxidase 1 2.4


25 415558AA885143Hs.125719ESTs 2.4


428141D50402Hs.182611solute carver family 2.4
11 (proton-coupled


406953L36847 gb:Human (clone p17190)rearrangediduro2.4


444471A8020684Hs.11217KIAA0877 protein 2.4


451031A1360187Hs.4254ESTs 2.4


30 455302AW997641 gb:RC6-BN0052-170200-011-DO62.4
BN0052 Homo


449063AI627352Hs.236547Homo Sapiens, clone 2.4
IMAGE:2905978, mRNA,


401048 2.4


434420AA688278Hs.194864hypothetical protein 2.4
FLJ22578


425848BE242709Hs.159637valyl-tRNAsynthetase2 2.4


35 449086AI628357Hs.208037ESTs 2.4


415238837780Hs.21d22ESTs 2.4


448337AW206453Hs.3782ESTs 2.4


416991N36389Hs.141296KIAA0226 gene product 2.3


412600L28824Hs.74101spleen tyrosine kinase2.3


418385AW590613Hs.301040Homo Sapiens, clone 2.3
IMAGE:3357127, mRNA,


440769BE561793Hs.21446KIAA1716 protein 2.3


450437X13956Hs.24998hypothetical protein 2.3
MGC10471


412035N78559Hs.293629hypothetical protein 2.3
MGC3121


406739AI566709Hs.182426ribosomal protein S2 2.3


418506AA084248Hs.85339G protein-coupled receptor392.3


410286A1739159Hs.61898DKFZP586N2124 protein 2.3


443740856434Hs.21062ESTs 2.3


405605 2,3


416913AW934714 gb:RCi-DT0001-031299-011-all2.3
DT0001 Homo


426509M31166Hs.2050pentaxin-related gene,2.3
rapidly induced b


445828F05802Hs.81907ESTs 2.3


457195A8011099Hs.196647KIAA0527 protein 2.3


420372AW960049Hs.293660Homo Sapiens, clone 2.3
IMAGE:3535476, mRNA,


423198M81933Hs.1634cell division cycle 2.3
25A


55 457730AW753613 gb:RC1-CT0268-060100-013-e012.3
CT0268 Homo


412014AI620650Hs.43761ESTs, Weakly similar 2.3
to A46010 X-linked


447131NM Hs.17466retinoic acid receptor2.3
004585 responder (tazaro


446288AW189209Hs.149708ESTs 2.3


436954AA740151Hs.130425ESTs 2
3


411658AW855598 gb:CM1-CT0278-031199-032-e06.
CT0278 Homo 2.3


404240 2,3


456094H95091 gb:yw57a09.r1 5oares_placenta2.3
Bto9weeks_


416951AA190926Hs.190785ESTs, Moderately similar2.3
to S65657 alpha


406737AI356586 gb:qy15h09.x1 NCI 2.3
CGAP
Brn23 Homo sapien


65 458453A1097452Hs.135095_ 2.3
_
ESTs


452330AI879127Hs.191979KIAA1733 protein 2.3


408523AW833259Hs.314287ESTs 2.3


455470AW947992 gb:PMO-MT0011-240300-001-c092.3
MT0011 Homo


436323817697Hs.1d0963ESTs, Weakly similar 2.3
to 138022 hypotheti


450000AI952797Hs.10888hypothetical protein 2.3
FLJ21709


416171H23896Hs.125790leucine-rich repeat-containing2.3
2


419134T89863Hs.221771ESTs 2.3


445933AV655733Hs.293860spinster-like protein 2.3


422089AA523172Hs.103135ESTs, Weakly similar 2.3
to SFR4
HUMAN SPLIC


75 449911AI262106Hs.12653_ 2.3
ESTs


417079U65590Hs.81134interleukin 1 receptor2.3
antagonist


411742AW247593Hs.71819eukaryotic translation2.3
initiation factor


435615Y15065Hs.4975potassium voltage-gated2.3
channel, KOT-lik


423491AA191765Hs.129673eukaryolic translation2.3
initiation factor


8~ 407182AA312551Hs.230157ESTs 2.3


411448AA178955Hs.271439ESTs, Weakly similar 2.3
to 138022 hypothe6


438644A1126162Hs.129037ESTs 2.3


432691U29725Hs.3080mitogen-activated protein2.3
kinase 7


181


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
452198A1097560Hs.61210ESTs, Weakly similar 2.3
to 138022 hypothefi


4i AA151647Hs.68877cytochrome b-245, alpha2.3
1125 polypepfide


404054 2.3


430458AA479300Hs.225706ESTs, Weakly similar 2.3
to 138022 hypothefi


440210AW674562Hs.125296ESTs 2.3


446727ABOt Hs.16032KIAA0523 protein 2.3
1095


453775NM Ns.35120replication factor 2.3
002916 C (acfivator 1) 4
(37


438379N23018Hs.i71391Gterminal binding protein2.3
2


449919AI674685Hs.200141ESTs 2.3


1 415293849462Hs.106541ESTs 2.3
~


441126NM Hs.323715methionine adenosylUansterase2.3
000429 I, alpha


408203AA053137Hs.42390nasopharyngeal carcinoma2.3
suscepfibility


434941AW073202Hs.334825Homo Sapiens cDNA FWi47522.3
fis, clone NT


450748AI733093Hs.130016ESTs 2.3


1 404185 2.3



418327U70370Hs.84i36paired-like homeodomain2.3
transcription (a


451370AI791929Hs.300782ESTs 2.3


400034 2.3


407723AW071161Hs.252873ESTs 2.3


2O 431320AW969474Hs.183070ESTs 2.3


429271AF039850Hs.198515dead ringer (Drosophila)-like2.3
t


453707AW003879Hs.126522Homo Sapiens, clone 2.3
MGC:16722, mRNA, com


419225U70073 gb:HSU70073 Human Homo2.3
Sapiens cDNA clon


444656AI277924Hs.145199ESTs 2.3


25 405741 2.3


400917 2.3


432567AA736777Hs.293770ESTs 2.3


437949U78519Hs.4i654ESTs, Weakly similar 2.3
to A46010 X-linked


450514AC005785Hs.25059A kinase (PRKA) anchor2.3
protein 8


30 418400BE243026Hs.301989KIAA0246 protein 2.3


444019BE173977Hs.10098putative nucleolar 2.3
RNA helicase


406326 2.3


412077N51107Hs.47199ESTs, Weakly similar 2.3
to F1J00004 protein


427647W19744Hs.i80059Homo Sapiens cDNA FLJ206532.3
fis, clone KA


35 414528AA148950Hs.lB$836ESTs 2.3


414854BE546797Hs.51483ESTs, Weakly similar 2.3
to hypothetical pro


420352BE258835 gb:6011 17374F1 NIH 2.3
MGC_16 Homo Sapiens
c


439467AW29227Hs.158365ESTs 2.3
5


402627 2.3


4O 451711AK000461Hs.26890cat eye syndrome chromosome2.3
region, cand


424308AW975531Hs.154443minichromosome maintenance2.3
deficient (S.


423869BE409301Hs.134012C1q-related factor 2.3


405915 2.3


431503NM Hs.258576claudin 12 2.3
012129


45 423306W88562Hs.108198ESTs 2.3


443232AF16t52tHs.908tphenylalanyl-tRNASynthetasebeta-subuni2.3


433064D79991Hs.30002SH3-containing protein2.3
SH3GLB2; KIAAt848


434437AI9t2566Hs.187813ESTs 2.3


436191BE407866Hs.170253hypotheficalprotein 2.3
FLJ23282


SO 420006H14429Hs.94300serologically defined 2.3
colon cancer anfig


447942Ft2628Hs.334786hypotheficalprotein 2.3
MGC16040


403166 2.3


422119AI277829Hs.111862KIAA0590 gene product 2.3


403751 2.3


55 426451AI908165Hs.169946GATA-binding protein 2.3
3


427413BE547647Hs.t77781hypothetical protein 2.3
MGC56t8


409091AW970386Hs.269423ESTs 2.3


440491835252Hs.24944ESTs, Weakly similar 2.3
to 2109260A B cell


427722AKOOOi23Hs.180479hypothetical protein 2.3
FLJ20116


6O 405747 2.3


438210AA780519Hs.311601EST 2.3


404652 2.3


423524AF055989Hs.129738potassium voltage-gated2.2
channel, Shaw-re


426793X89887Hs.172350HIR (histone cell cycle2.2
regulafion defer


65 444424AI654684Hs.196377ESTs 2.2


434031BE384165Hs.23723pseudouridylate synthase2.2
1


427650AW501245Hs.252259ribosomal protein S3 2.2


435220D50030Hs.104HGF activator 2.2


438279AA805166Hs.154762HIV-1 rev binding protein2.2
2


7O 424668D83702Hs.i5t573cryptochrome 1 (photolyase-like)2.2


429961BE246829Hs.226770DKFZP566C0424 protein 2.2


442065A183t229Hs.128417hypotheficalprotein 2.2
FLJ14009


415198AW009480Hs.943natural killer cell 2.2
transcript 4


420536AL117455Hs.275438histone deacetylase 2.2
7A


75 411263BE297802Hs.69360kinesin-like 6 (mitotic2.2
cenUomere-assoc


443753AW367578Hs.134749ESTs 2.2


423243AA351938Hs.23964sin3-associated polypeptide,2.2
lBkD


446572AV659t51Hs.282961ESTs 2.2


4t AF022375Hs.73793vascular endothelial 2.2
2247 growth (actor


$O 421040AA715026Hs.135280ESTs 2.2


426212571824Hs.167988neural cell adhesion 2,2
molecule 1


455584BE007420 gb:PM3-BN0142-200300-001-c042.2
BN0142 Honro


406851AA609784Hs.180255major histocompafibility2.2
complex, class


182


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
444153AK001610Hs.10414hypothetical protein 2.2
FLJ10748


419575043431Hs.91175topoisomerase (DNA) 2.2
III alpha


418672L44284Hs.159743ESTs 2.2


456261AA210718Hs.104157ESTs. Weakly similar 2.2
to KIAA0694 protein


415737AAi67626Hs.118743ESTs 2.2


447554A1391598Hs.36119ESTs, Weakly similar 2.2
to ALU1 HUMAN ALU
S


405159 2.2


442177AW661820Hs.211413ESTs 2.2


446139H77395Hs.39749ESTs 2.2


10458339AW976853Hs.i72843ESTs 2.2


401876 2.2


439566AF086387 gb:Homo Sapiens full 2.2
length insert cDNA


425079H09963Hs.2257vitronecfin (serum 2.2
spreading factor,
som


441837AA361743Hs.179881core-binding factor, 2.2
beta subunit


1 430644AB015419Hs.247710preproprolacfin.releasing2.2
s pepfide


431474AL133990Hs.190642ESTs 2.2


407739NM Hs.38070Lymphoid nuclear protein2.2
002285 related to AF4


424244AV647184Hs.143601hypolhefical protein 2.2
hCLA-iso


438057AW294544Hs.125785ESTs, Weakly Similar 2.2
to CORB MOUSE CORNI


20412715NM Hs.74519primase, polypepfide 2.2
000947 2A (58kD)


422365AF035537Hs.115521REV3 (yeast homology-like,2.2
catalytic sub


404170 2.2


406902M32074 gb:Human refinoic acid2.2
receptor gamma 2


437902AA770599Hs.144055ESTs 2.2


25401012 z.2


446502AI302654Hs.208024ESTs 2.2


442554AW467376Hs.129640ESTs 2.2


443021AA368546Hs.8904Ig superfamily protein2.2


421141AW117261Hs.125914ESTs 2.2


30443070BE388662Hs.8984Homo Sapiens chromosome2.2
14 BAC 98L12


446566H95741Hs.17914membrane-spanning 4~omains,2.2
subfamily A


427695888483Hs.172862ESTs 2.2


426503AA380153 gb:EST93093 Skin tumor2.2
I Homo Sapiens cD


431468AW248431Hs.256526nuclear prelamin A 2.2
recognifion factor


35416185AW975861Hs.47367KIAA1785protein 2.2


437319BE410958Hs.56406Homo Sapiens cDNA FLJ 2.2
13549 fis, clone PL


402064 2.2


413335AI613318Hs.48442ESTs 2.2


408212AA297567Hs.43728hypothetical protein 2.2


40aosls9 z.2


451099852795Hs.25954interleukin 13 receptor,2.2
alpha 2


407335AA631047Hs.158761Homo Sapiens cDNA FLJ 2.2
13054 fis, clone NT


409715W42591Hs.23892ESTs 2.2


431921N46466Hs.58879ESTs 2.2


45443823BE089782Hs.9877hypothetical protein 2.2


432458AI968598Hs.78768malignant cell expression-enhanced2.2
gene!


419726050330Hs.1274bone rtrorphagenelic 2.2
protein 1


423178A1033140Hs.124983Homo Sapiens mRNA; 2.2
cDNA DKFZp564C142
(fr


451089AA903705Hs.4190Homo Sapiens cDNA: 2.2
FLJ23269 fis, clone
C


SO415216AI825905Hs.193211Homo Sapiens cDNA FLJ114212.2
fis, clone HE


442242AV647908Hs.90424Homo Sapiens cDNA: 2.2
FLJ23285 fis, clone
H


441830AA383104Hs.42954hypotheficalprotein 2.2
DKFZp564D0372


406660X65371Hs.172550polypyrimidine tract 2.2
binding protein (he


443378AW392550Hs.9280proteasome (prosome, 2.2
macropain) subunil,


432558897268Hs.177269ESTs 2.2
5


408146845621Hs.81057hypothetical protein 2.2
MGC2718


419865NM Hs.93502Ut-snRNP binding protein2.2
007020 homolog (70kD)


439444AI277652Hs.54578ESTs, Weakly similar 2.2
to 138022 hypotheti


438407AI457122Hs.129673eukaryotic Uanslafion 2.2
initiafion factor


60450184W31096Hs.237617Homo Sapiens, clone 2.2
IMAGE:3447394, mRNA,


409130BE076601Hs.75658phosphorylase,glycogen;brain2.2


428844AW972635Hs.301904hypolhefical protein 2.2
FLJ12671


429489AF008203Hs.204039aristaless-like homeobox2.2
3


433042AW193534Hs.281895Homo Sapiens cDNA FLJ116602.2
fis, clone HE


65440658H29142Hs.143032ESTs, Weakly similar 2.2
to neuronal thread


408204AA454501Hs.43666protein tyrosine phosphatase2.2
type IVA, m


427498NM Hs.178728methyl-CpG binding 2.2
003926 domain protein 3


408006H57654Hs.303345ESTs, Weakly similar 2.2
to 138022 hypolhefi


445703AV654845Hs.27glycine dehydrogenase 2.2
(decarboxylafing;


70431446AW294929Hs.255369Homo Sapiens cDNA FLJ 2.2
10265 fis, clone HE


456660AA909249Hs.112282solute comer family 2.2
30 (zinc transport


433099NM Hs.3187nuclear transcripfion 2.2
002504 factor, X-box bind


415857AA866115Hs.127797Homo Sapiens cDNA FW 2.2
11381 fis, clone HE


415245N59650Hs.27252ESTs 2.2


75443657814973 gb:yf42t10.s1 Scares 2.2
fetal liver spleen


402521AW501216Hs.108945KIAA0515 protein 2.2


414819BE177320Hs.156148hypothetical protein 2.2
FLJ13231


446530AV658909Hs.282642ESTs 2.2


415797A1291896Hs.72800ESTs 2.2


80414812X72755Hs.77367rtronokine induced 2.2
by gamma interferon


453028A8006532Hs.31442Recd protein-like 4 2.2


412133083460Hs.73614solute carver family 2.2
31 (copper Vanspo


407881AW072003Hs.40968heparan sulfate (glucosamine)2.2
3-0-sulfot


183


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
437033AW248364Hs.5409RNA polymerase I subunit2.2


422732AA577455Hs.24937transformer-2 alpha 2.2
(htra-2 alpha)


416388AI417358Hs.73677ESTs 2.2


452849AF044924Hs.30792hook2 protein 2.2


446615BE513202Hs.15589PPAR binding protein 2.2


428361NM Hs.183858transcriptional intermediary2.2
015905 factor 1


446279AA490770Hs.182382ESTs 2.2


422938NM_001809Hs.1594centromere protein 2.2
A (l7kD)


403969 2.2


1 410423AW402432Hs.63489protein tyrosine phosphatase,2.2
~ non-recept


429736AF125304Hs.212680tumor necrosis factor2.2
rerxptor superfami


447091AW089648Hs.157779ESTs, Weakly similar 2.2
to CA17-HUMAN COLLA


422017NM Hs.110776STAT induced STAT 2.2
003877 inhibitor-2


426728NM Hs.171957hiple functional domain2.2
007118 (PTPRF interact


15 438726A8033103Hs.6385KIAA1277 protein 2.2


453315BE544203Hs.24831ESTs 2.2


423244AL039379Hs.209602ESTs, Weakly similar 2.2
to ubiquitous TPR
m


433610AA806822Hs.112547ESTs 2.2


429451BE409861Hs.202833heme oxygenase (decycling)2.2
1


417980832235 gb:yh67f08.r1 Soares 2.2
placenta Nb2HP Homo


4pt~7 2.2


414406BE297904 gb:601177814F1 NIH 2.2
MGC_17 Homo Sapiens
c


401827 2.2


446913AA430650Hs.i6529transmembrane 4 superfamily2.2
member (tetr


25 452294AI871925Hs.117895ESTs, Moderately similar2.2
to A47582 B-cel


404084 2.2


456786AK002084Hs.132851hypothetical protein 2.2
FLJ11222


435031AI632091Hs.116877ESTs 2.2


442609AL020996Hs.8518selenoprotein N 2.1


439732AW629604Hs.167641hypothetical protein 2.1
from EUROIMAGE 1703


421506BE302796Hs.105097thymidine kinase 1, 2.1
soluble


439253AF086064Hs.332252ESTs 2.1


409669AW177551Hs.220255hypothetical protein 2.1
MGC13098


429574BE268321Hs.208912hypothetical protein 2.1
MGC861


35 437470AL390147Hs.134742hypothetical protein 2.1
DKFZp547D065


408945AW015089Hs.4964DKFZP586J1624 protein2.1


447687A1627947Hs.150186hypotheticalprotein 2.1
DKFZp566K1946


459584A1910884Hs.207898ESTs 2.1


439130AA306090Hs.124707ESTs 2.1


4~ 428180A1129767Hs.182874guanine nucleotide 2.1
binding protein (G
pr


442028AI239437Hs.48945ESTs 2.1


430968AW972830 gb:EST384925 MAGE 2.1
resequences, MAGL
Homo


443609AV650231Hs.282941ESTs, Highly similar 2.1
to A Chain A, Human


417164AA338283Hs.81361heterogeneous nuclear2.1
ribonucleoprotein


45 444534AW271626Hs.42294ESTs 2.1


438391AI262248Hs.25027ESTs 2.1


442003AW297497Hs.201891ESTs 2.1


456278BE300369Hs.289038hypothetical protein 2.1
MGC4126


416976BE243985Hs.80680major vault protein 2.1


417810D28419Hs.82609hydroxymethylbilane 2.1
synthase


445242BE156478Hs.21108ESTs, Weakly similar 2.1
to ALU1 HUMAN ALU
S


452712AW838616 gb:RCS-LT0054-140200-013-D012.1
LT0054 Homo


434926BE543269Hs.50252mitochondrial ribosomal2.1
protein L32


421564AB007864Hs.105850KIAA0404 protein 2.1


55 424927AW973666Hs.153850hypothetical protein 2.1.
C321D2.4


432742AA564453Hs.162339ESTs 2.1


435958H98180Hs.117975ESTs 2.1


421531AA713505Hs.291769ESTs 2.1


410431BE261320Hs.158196transcriptional adaptor2.1
3 (ADA3, yeast h


()O420503AI570943Hs.337546ESTs 2.1


448127A1478416Hs.282883ESTs, Weakly similar 2.1
to ALU1 HUMAN ALU
S


452897BE066058Hs.269233ESTs, Moderately similar2.1
to 178885 serin


447112H17800Hs.7154ESTs 2.1


406577 2.1


65 437162AW005505Hs.5464thyroid hormone receptor2.1
coactivating pr


451460AI797550Hs.209652ESTs 2.1


447402H5452CHs.18490hypotheticalprotein 2.1
F1J20452


435828AA700705Hs.13852ESTs 2.1


436396A1683487Hs.152213wingless-type MMTV 2.1
integration site
fami


420582BE047878Hs.99093Homo Sapiens chromosome2.1
19, cosmid 82637


452020AA722012Hs.255757ESTs, Weakly similar 2.1
to AT2A HUMAN POTEN


415586245481 gb:HSC20E041 normalized2.1
infant brain cDN


452620AA436504Hs.119286ESTs 2.1


4570668E244613Hs.158272ESTs, Weakly similar 2.1
to CA13 MOUSE COLLA


75 435472AW972330Hs.283022triggering receptor 2.1
expressed on myeloid


431741AA514783Hs.191701ESTs 2.1


446840AW294828Hs.209203ESTs 2.1


440818AI147060Hs.146726ESTs 2.1


410174AA306007Hs.59461DKFZP434C245 protein 2.1


80 400822 2.1


412760AW379030Hs.41324ESTs 2.1


410653BE383768Hs.6523895 kDa retinoblastoma2.1
protein binding pr


426925NM_tH11196Hs.315689Homo Sapiens cDNA: 2.1
FLJ22373 fis, clone
H


184


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
424242AA337476Hs.293984hypothefiral protein 2.1
MGC13102


452560BE077084Hs.336432ESTs 2.1


456437A1924228Hs.115185ESTs, Moderately similar2.1
to PC4259 ferti


458922BE501831Hs.282053ESTs 2.1


439231AW581935Hs.141480Homo Sapiens mRNA; 2.1
cDNA DKFZp434N079
(fr


419488AA316241Hs.90691nucleophosmin/nucleoplasmin2.1
3


411829AW865749 gb:OV3-SN0021-100500-185~c032.1
SN0021 Homo


457192AL135682Hs.22452Homo Sapiens mRNA 2.1
for KIAA1737 protein,


422128AW881145 gb:OVO-OT0033010400-182-a072.1
OT0033 Homo


1 452571W31518Hs.34665ESTs 2.1
~


423699H41850Hs.131846PCAF associated factor2.1
65 alpha


406610 2.1


453638AW814996 gb:MR1-ST0206-170400-024-h092.1
ST0206 Homo


418856AA362858 gb:EST72900 Ovary 2.1
II Homo Sapiens cDNA
5


I 437623D63880Hs.5719chromosome condensation-related2.1
S SMGasso


410908AA121686Hs.10592ESTs 2.1


420221N25991Hs.43725ESTs 2.1


424739AA346108Hs.221610ESTs 2.1


425398AL049689Hs.156369hypothetical protein 2.1
similar to lenascin


424901111933Hs.182505POU domain, class 2.1
3, transcripfion
facto


411096U80034Hs.68583mitochondrial intermediate2.1
pepfidase


415635F13168 gb:HSC3JF101 normalized2.1
infant brain cDN


418181U37012Hs.83727cleavage and polyadenylafion2.1
specific fa


407103AA424881Hs.256301hypothefical protein 2.1
MGC13170


25 454389AW752571 gb:IL3-CT02t3-170100-055-F022.1
CT0213 Homo


400021 2.1


439228N51700 gb:yy72d01.s1 Soares_mulGple_sclerosis-2.1


456505AA504595Hs.111418ESTs 2.1


405258 2.1


444645AI184564Hs.101654ESTs 2.1


430246A1269069Hs.109268hypothefical protein 2.1
FLJ12552


458687AW024815Hs.170088GLUT4 enhancer factor2.1


403857 2.1


400258 2.1


35 422221AA306649Hs.169370FYN oncogene related 2.1
to SRC, FGR YES


441054AA913591Hs.126480ESTs 2.1


452700AI859390Hs.288940five-span Vansmembrane2.1
protein M83


454606AW809752 gb:MR4-ST0124-181299-020-b062.1
ST0124 Homo


448954A8014564Hs.22616KIAA0664 protein 2.1


443148A1034357Hs.211194ESTs, Weakly similar 2.
to ALUB HUMAN ALU t
S


453486AL039201Hs.173554ubiquinol-cytochrome 2.1
c reduclase core
pr


437695AA769202Hs.192142ESTs 2.1


425449X52056Hs.157441spleen focus forming 2.1
virus (SFFV) prow


447270AC002551Hs.331general transcripfion2.1
factor IIIC, polyp


45 435677AA694142Hs.293726ESTs, Weakly similar 2.1
to TSGA RAT TESTIS


436382AW977063Hs.250181ESTs 2.1


435837AI689210Hs.187276Homo Sapiens cDNA 2.1
FLJ11431 fis, clone
HE


458287AA987556Hs.12867ESTs 2.1


423794BE551781Hs.231895ESTs 2.1


408049AW076098Hs.74316desmoplakin (DPI, 2.1
DPII)


402721 2.1


451999AW176401Hs.27424DEADIH (Asp-Glu-Ala-AspIHis)2.1
box polypep


417541AI992191Hs.180040hypotheficat protein 2.1
F1J22439


414857AW402389Hs.920modulator recognifion2.1
factor I


435760AF231922Hs.213004chromosome 21 open 2.1
5 reading frame 62


428086AL110193Hs.224137hypotheticalprotein 2.1


447853A1434204Hs.164285ESTs, Weakly similar 2.
to AFG1 YEAST AFG1 t


419034NM_002110Hs.89555hemopoiefic cell kinase2.1


431019NM Hs.2714forkhead box G18 2.1
005249


()~421064AI245432Hs.101382turtror necrosis (actor,2.1
alpha-induced pro


416435AI431301Hs.179703KIAA0129 gene product2.1


437014AA808757Hs.222531ESTs, Weakly similar 2.1
to S59501 intertero


459369T83080 gb:yd40e03.r1 Soares 2.1
fetal liver spleen


402239 2.1


65 412280AW205116Hs.272814hypothefical protein 2.1
DKFZp434E1723


426012AA367507Hs.75874pregnancy-associated 2.1
plasma protein A


438885AI886558Hs.184987ESTs 2.1


426076AW962714 gb:EST374787 MAGE 2.1
resequences, MAGG
Homo


404561 2.1


442932AA457211Hs.8858bromodomain adjacent 2.1
to zinc finger doma


408175W29089Hs.19066hypothefical protein 2.1
DKFZp66702416


423867AA331886 gb:EST35757 Embryo, 2.1
8 week I Homo sapien


458604W37944Hs.4007Sarcolemmat-associated2.1
protein


409650T08490Hs.288969HSCARG protein 2.1


75 401729 2.1


433675AW977653Hs.75319ribonucleotide reductase2.1
M2 polypepfide


456741W37608Hs.184492ESTs 2.1


417037BE083936Hs.80976anfigen idenfified 2.1
by monoclonal anfitx~d


415079843179Hs.22895hypothefical protein 2.1
FLJ23548


439262AA832333Hs.333045ESTs 2.1


403108 2.1


436718AW015227Hs.289053hypothetical protein 2.1
FLJ14733


440696AI762757Hs.187660putative RabS GDP/GTP2.1
exchange factor ho


Igs


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
409745AA077391 gb:7B14E12 Chromosome2.1
7 Fetal Brain cDNA


453485BE620712Hs.33026hypotheficalprotein 2.1
PP2447


418177N44967Hs.5663ESTs 2.1


457292A1921270Hs.334882hypotheficalprotein 2.1
FLJ14251


454434AA083558Hs.261286ESTs 2.1


406085 2.1


424441X14850Hs.147097H2A histone family, 2.1
member X


422726011690Hs.1572faciogenital dysplasia2.1
(Aarskog-Scott sy


424576BE154142Hs.96833ESTs 2.1


423660AL045228Hs.130831Homo Sapiens mRNA; 2.1
cDNA DKFZp434L137
(fr


403509AF231919Hs.18759KIAA0539 gene product2.1


441940AW298115Hs.128152ESTs 2.1


439190AW978693Hs.293811ESTs 2.1


417791AW965339Hs.i11471ESTs 2.1


1 423701AA329856Hs.143022ESTs 2.1
5


427239BE270447Hs.174070ubiquitin cartier 2.1
protein


459642BE243103 gb:TCAAP2E0949 PediaUic2.1
acute myelogeno


450385AI631024Hs.24948synuclein, alpha interacfing2.1
protein (sy


425159NM Hs.154868carbartroyl-phosphate2.1
004341 synthetase 2, aspart


425591AW294734Hs.279727Homo Sapiens cDNA 2.1
FLJ14035 fis, clone
HE


445101T75202Hs. Homo Sapiens mRNA; 2.1
1 cDNA DKFZp586C1019
2314 (f


412811H06382Hs.21400ESTs 2.1


426369AF134157Hs.169487Kreisler (mouse) maf-related2.1
leucine zip


435924AW029203Hs.191952ESTs 2.1


418388872332Hs.29258Homo Sapiens cDNA 2.1
FLJ11364 fis, clone
HE


452235AL039743Hs.28514testes development-related2.1
NYD-SP21


452313Y00486Hs.28914adenine phosphorlbosyltransterase2.1


450704H85157Hs.40696_ 2.1
ESTs


427539AA405205Hs.97960ESTs, Weakly similar 2.
to T51146 ring-box t


4o2oz6 2.1


405362 2.1


414718H95348Hs.107987ESTs 2.1


433424868252Hs.163566ESTs 2.1


444875A1200759Hs.44737ESTs 2.0


3 449523NM Hs.54443chemokine (GC motif) 2.0
S 000579 receptor 5


456072H54381 gb:yq89a03.s1 Soares 2.0
fetal liver spleen


436331AI239495Hs.120189ESTs 2.0


448418243704Hs.21192Homo sapiens clone 2.0
25155 mRNA sequence


447250AI878909Hs.17883protein phosphatase 2.0
1G (formerly 2C),
ma


448192843915Hs.4958ESTs 2.0


448966AW372914Hs.86149phosphoinositol 3-phosphate-binding2.0
prot


408605AF025374Hs.46465T-cell, immune regulator2.0
1


410790AW803357 gb:IL2-UM0079-090300-050-A082.0
UM0079 Homo


436872X15624 gb:Human H1 RNA 2.0


432238AL133057Hs.274135Homo Sapiens mRNA; 2.0
cONA DKFZp434K1815
(f


446307T50083Hs.9094ESTs 2.0


436588AA759233Hs.126506ESTs 2.0


452487AW207659Hs.6630Homo Sapiens cDNA 2.0
FLJ13329 fis, clone
OV


430420AW140027Hs.26373Homo Sapiens cDNA: 2.0
FLJ23449 fis, clone
H


432036AF224266Hs.272373interleukin 20 2.0


414460L00727Hs.898dystrophic myotonica-protein2.0
kinase


433507AI817336Hs.191791ESTs 2.0


427964AA418082Hs.98286ESTs, Weakly similar 2.0
to T20655 hypotheti


443108W86975Hs.203707ESTs 2.0


434504A1887341Hs.121590hypothetical protein 2.0
FLJ12827


454310AW818390Hs.175613homolog of Xenopus 2.0
Gaspin


443566AI290284Hs.159872ESTs 2.0


449722BE280074Hs.23960cyclin B1 2.0


452682AA456193Hs.9071progesterone membrane2.0
binding protein


412362AW945484Hs.184252ESTs, Weakly similar 2.0
to ALUB HUMAN ALU
S


429341X73874Hs.2393phosphorylase kinase,2.0
alpha 1 (muscle)


435863AF255346Hs.62919Jun dimerlzation protein2.0
p2ISNFT


400774858624Hs.2186eukaryo6c translation2.0
elongation factor


453944AW975369Hs.292570Homo Sapiens, clone 2.0
IMAGE:3502107, mRNA,


419227BE537383Hs.89739chotinergic receptor,2.0
nicotinic, beta po


448529T26460Hs.22550ESTs 2.0


443206AB011420Hs.9075serlnetthreonine kinase2.0
17a (apoplosis-i


439360AA448488Hs.336629rlbasomal protein 2.0
L44


436660AI658870Hs.184513ESTs 2.0


449030A1365582Hs.57100Homo Sapiens mRNA 2.0
for FW00016 protein,


411048AK001742Hs.67991hypothetical protein 2.0
DKFZp434G0522


406624AF052762 gb:Homo Sapiens clone2.0
csneg8-1 immunoglo


450666T99968Hs.18799ESTs, Weakly similar 2.0
to 138022 hypotheti


4461438E245342Hs.306079sec61 homolog 2.0


437698861837Hs.7990ESTs, Moderately similar2.0
to 184505 catci


426607AA382330Hs.124223ESTs 2.0


449246AW411209Hs.23363hypothefical protein 2.0
FLJ10983


422564AI148006Hs.222120ESTs 2.0


432682A1376400Hs.159588ESTs 2.0


422140BE295918Hs.i mutS (E. coli) homolog2.0
121935


408215BE614290Hs.43812syntaxin 10 2.0


417129A1381800Hs.300684calcitonin gene-related2.0
peptide-receptor


442772AW503680Hs.5957Homo Sapiens clone 2.0
24416 mRNA sequence


186


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
434928AWOi Hs.4267Homo Sapiens clones 2.0
5595 24714 and 24715 mRNA


411380AW84t619 gb:RCi-CN0017-120200-012-b09CN00172.0
Homo


430603AA148164Hs.247280HBV associated factor 2.0


425905AB032959Hs.318584novel C3HC4 type Zinc 2.0
finger (ring finge


401 2.0
t
25


412939AW411491Hs.2186eukaryofic Uanslation 2.0
elongafion (actor


448740BE250632Hs.8026sestrin 2 2.0


454390A80207t3Hs.56966KIAA0906 protein 2.0


415012NM Hs.77793c-sro tyrosine kinase 2.0
004383


1 410407X66839Hs.63287carbonic anhydraselX 2.0
~


403478 2.0


456485AI393037Hs.97871Homo Sapiens, clone 2.0
IMAGE:3845253, mRNA,


430294AI538226Hs.32976guanine nucleotide 2.0
binding protein 4


411669BE612676Hs.303isUomal cell-derived 2.0
16 factor 2-like 1


15451944AW4452t8Hs.210876ESTs 2.0


436395AJ227900 gb:Homo Sapiens partial2.0
mRNA; ID EE2-168


456457AA252905Hs.194477E3 ubiquifin ligase 2.0
SMURF2


449123050920Hs.23t06KIAA0130 gene product 2.0


409214AW405967Hs.333388Homo Sapiens, clone 2.0
IMAGE:3957135, mRNA,


437619AW351491Hs.334853hypothefical protein 2.0
FLJ23544


453348BE272318Hs.8595hypothetical protein 2.0
FU12438


424382AA35i898Hs.23539ESTs 2.0


447079AA280057Hs.105280ESTs, Weakly similar 2.0
to dJ~3K23.2 [H.sa


449501AI652924Hs.231942ESTs 2.0


25422893X98411Hs.121555myosin IF 2.0


412125Yl7t Hs.73393eyes absent (Drosophila)2.0
14 homotog 4


434845BE267057Hs.325321hypotheficalprotein 2.0
832184 1


410422AL042014Hs.334698Homo Sapiens, clone 2.0
MGC:15203, mRNA, com


430255AK000703Hs.323822Homo Sapiens mRNA for 2.0
KIAA1551 protein,


451656BE327088Hs.212752ESTs 2.0


442068BE3t2873Hs.314932ESTs 2.0


446646AW197626Hs.271901ESTs. Moderately similar2.0
to S08686 finge


442690A1014727Hs.160047ESTs, Weakly similar 2.0
to 828096 line-1 pr


454277AW295069Hs.31743ESTs, Weakly similar 2.0
to 1157 HUMAN ZINC


3 426910AA470023Hs.190089ESTs, Moderately similar2.0
S to ALUt HUMAN A


402798 2.0


404554 2.0


TABLE 9B:
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
Pkey CAT Number Accession
45 407909 1025254 1 AW103986 BEi56395 BE156391 BE156190 BE156184 BE156388
BE156394
408432 1058667 1 AW195262 827868 AW81 1262
409193 110747 1 AA131483 AA065t56 AA076448
409745 115237 1 AA077391 A1347618 A1361453 A1088754 AW207491 AW960912 AA921874
AA286833 AA150722 BE152353 AW 188822 BE152450
410447 1203929_1 AW816134 BE063456 AW748795 BE150839
410790 1221131 1 AW803357 AW803423 AW812233 806814
411256 1236790 1 AW834039 AW834040 AW834047 AW845410 BE003128 AW852479
411380 1242343_1 AW84t6t9AW851958AW851851AW851985
411632 1252361 t AW854829 AW854805 AW854841 AW854825 AW854822 AW854830
AW854835 AW854826
4i 1658 1252987 1 AW855598 AW855608 BE148763 BEt48764 AW855645 AW855615
AW855596 AW855610 AW85560t AW855605
55 411829 1260309 1 AW865749 BE1794t9 BE179492
412225 1284108 1 AW902042 N77591
4t 2370 1291952 1 AW946614 AW946622 AW946663 AW946667 AW946615 AW946619
412391 12926251 AW9477t0AW947698AW947697AW947713
413257 1355963 1 BE075035 BE074999 BE075006 BE075005 BE075032 BE075008
BE075037
()~ 413604 1379715 1 851767 8E152515 244834 H23397
414406 1443333 1 BE297904 BE294312
414550 1460990_-1 BE379808
415346 1534581 t 243108 F06295 813085
415406 1536026 1 T26510 F07926 853367
65 415586 1540116 1 245481 F12393T74437
415635 1540853_1 F13168 821289 T77628
416871 1626761 1 H987t6 N90792 N24283
416913 163001 1 AW934714 BE161007 BEt62500AW749902 AW749864 BE162498 BE161005
AA190449 AW5t3465 BE16t006 BE162499
417980 1712954_1 832235 832247 832219
418333 173_2 W92113 AA702794 BE0443t6 W9t984 AA679375 T94184 AA679335 BE503t26
AW502118 BE467367 AA584550 AW139964 893353 AW088477
AI887846 AW502624 W81697 W8t696 AA447817 AA447667 F13631 AW268271 AA055366
AW629027 AA677404 AA83i6t8 AI124782 AA889402
AA765804 AA765530 AA055698 AA594019 AI267368 AA456946 893354 AF264624 AW668618
AA601493
418856 179649 1 AA362858 AW863761 AA229428
419217 182954 1 AA504571 AA235243 AA411737 AW969068 AA406543
75 419225 1830274 -1 U70073
419311 183793 1 AA689591 AW974261 AA236240 A1077451 AA63t399 AW974262
420352 192979 1 BE258835 AW968316 AA25891 B AW843305 814744 AI580388 BE071923
836280
422128 211994 t AW881145 AA490718 M85637 AA304575 T06067 AA33199i
422156 212379_1 N34524 AA305071 AW954803 AA502335 AI433430 AI203597 AW026670
AW265323 AW850787 AA317554 AW993643 AW835572 AW385512
AI334966 W32951 H62656 H53902 888904 AW835732
422176 212714 1 H80977 BE147695 AA305496 AW962366 AA436754
423756 231725 1 AA828125 AA834883 AA330555
423867 232732_1 AA331886 AW962659 AW962655 T89841
1g7


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
425189 247825 1 H16622 817322 AA351959
425517 252729 1 AF121179 BE162736 AA358827
426076 260504 1 AW962714 AA369277 AA369278
426413 266650 1 AA377823 AW954494 A1022688
426503 268283 1 AA380153 AA380233 AW963529
426531 268760 1 AA381071 AA381084 AA380862
429875 310034 1 A1091815 AA460162 AA460761
430968 326269 1 AW972830 AA527647 AA489820 AA570362
432088 341195 1 AA525454 H74039 889502 T77379
1 ~ 433532 368950 1 AW975367 AA598607 AA742735
434559 38889 1 AF147315 AW173079 T53029
435065 399329 1 BE064391 BE064395 AA663613 N99644
436190 41555 1 AK001059 AA633055
436395 41905 1 AJ227900 A1094933 AW051119 F00947
1 S 436532 421802 t AA721522 AW975443 T93070
436722 425758 1 AW975977 AA729469 AA747132
436872 42851 -i X15624
437034 431713 1 AA742643 AA808575 AW976668
439086 46852_1 AF085947 H70981 H78989
439228 47001 1 N51700 AF086051 N51792
439518 47334 1 W76326 AF086341 W72300
439546 47360 1 AF088056 W76297 W72448
439566 47387 1 AF086387 W77884 W72711
439710 47550 1 AF086543 W96291 W96225
25 443657 576685 1 814973 814967 A1081006
444168 593829 1 AW379879 A1126285 H12014
444386 604004 1 BE065183 A1144398 BE065367
451129 859870 1 BE072881 BE072946 A1762181
452712 928309 1 AW838616 AW838660 BE144343 A1914520 AW888910 BE184854 BE184784
453446 967533 1 BE299996 BE297115 BE270415 BE295214 BE296526
453638 975649_1 AW814996 AL047199 AW850979
453746 979731_1 AL120611 BE006190 BE006189
454377 114761 1 AA076811 AW814764
454389 115682 1 AW752571 AW847602 AA077979
3 S 454606 1226149 2 AW809752 AW810271 AW809944 AW810319 AW810215 AW810368
AW810167
454630 1227352_1 BE142075 BE142148 BE142189 AW816249 BEi42147 BE142002
BE142406 BE142094 BE142020 BE142074 BE142347 BE142000 BE142375
AW811189 BE142133
454631 1227443 1 AW811324 AW811325 AW811326 AW811333 AW811329 AW811328
AW811332 AW811339 AW811335
454679 1228929_1 AW813110 AW813113
454967 1247021 1 AW848276 AW848416 AW848160 AWB47945 AW847947 AW848063
AW848113
455023 1249188 1 AW850907 AW850901 AW850877
455302 1276542 1 AW997641 AW891777
455470 1292849_1 AW947992 AW947967 AW947950 AW947957 AW947953 AW947973
AW947966 AW947971 AW947947 AW947970 AW947995 AW947979 AW947952
AW947956
45 455514 1321649 1 AW983871 BE090302 AW983867 AW983845 AW983860 AW983853
AW983852
455530 1322298_1 AW984744 AW984759
455584 1334741 1 BE007420 BE007419 BE007421 BE007422
455778 1364506_1 BE088746 BE088802 BE088755 BE088876 BE088947 BE088881
BE088952
455908 1382301 1 BE156306 BE156188 BE156298 BE156377 8E156374
456072 1470256 1 H54381 H54463 BE393262
456094 1504780 1 H95091 001228
457374 328758 1 AA493662 AW897396 8E154814
457578 359618 -1 AA578027
55 457730 393905_1 AW753613 AW753857 BE150374 BE150693 BE150394 AA808851
AA650159 AA654653 BE150419
TABLE 9C:
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank
Idenfifier (GI) numbers. 'Dunham, et al.' refers to the publication enfified
'The DNA
sequence of human chromosome 22' Dunham, et al. (1999) Nature 402:489-495.
Strand: Indicates DNA strand from which exons were predicted.
Nt_position: Indicates nucleofide positions of predicted exons.
Pkey Ref Slrand N<_posilion
400822 7465000 Plus 186223-186402,186878-187275
65 400859 9757499 Minus 91888-92018,98131-98294,99474-99570
400917 7283186 Minus 173258-173631
400992 8096828 Plus 140390-140822
401012 7230838 Minus 736-1137
401048 7232177 Plus 132430-132761

401125 8570296 Minus 126863-126984
401324 9863791 Plus 234057-234174
401384 6850939 Minus 58360-58545
401558 7139678 Plus 103510-104090
401626 8575943 Minus 238100-238432
75 401676 9965536 Plus 3891-4691
401714 6715702 Plus 96484-96681
401729 8134856 Minus 90651-90878
401827 2262095 Plus 94725-94860,98452-98660
401876 8099107 Plus 9591396641
402028 7139781 Plus 88749-89237
402064 8117294 Plus 100159-100350.10(1445-100912
402239 7690131 Plus 38175-38304,42133-42266
402408 9796239 Minus 110326-110491
Igg


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
402424 9796344 Minus 64925-65073
402516 9798099 Minus 195342-195511
402604 9909420 Plus 20393-20767
402627 9931216 Plus 12136-12272,16487-16628,17654-17798,18494-18621,18933-
19089,20669-20790,21134-21298,22866-22973,23686-23820,26626-
26895,29279-29469
402721 8969253 Minus 144428-144715
402798 3355547 Plus 23596-23867
402856 9801288 Minus 90119-90411
403048 4210991 Plus 44275-44592,49656-49955
1 ~ 403108 8980955 Plus 93253-93667
403142 9444521 Plus 89286-90131
403166 9838127 Minus 67762-67940.6869568856,70394-70507
403478 9958258 Plus 116458-116564
403680 7331517 Minus 157184-157415
I 5 403751 7229815 Minus 158794-160929
403790 8084957 Minus 87826-87947,8983590002
403797 8099896 Minus 123065-125008
403857 7708910 Minus 2524-3408
403881 7710245 Minus 107250-107685,108924-109213
403961 7596976 Minus 110393-110603
403969 8569909 Plus 31237-31375,3240532506
404020 8655966 Minus 174449-174663
404054 3548785 Plus 66713-69175
404084 9944055 Plus 2795-2969
25 404108 8247074 Minus 63603-64942
404170 9930793 Plus 168836-169248
404185 4572584 Minus 129171-129327
404240 5002624 Minus 116132-116407,116653-116922
404295 9856663 Minus 75747-75947
404299 5738652 Minus 3826-4025
404366 9964977 Plus 96589-96801
404554 7243881 Plus 42637-42839
404561 9795980 Minus 69039-70100
404584 9857511 Plus 138651-139153
404569 9931665 Minus 32824-32985
404642 9796810 Plus 102999-103145
404652 9796969 Minus 108172-108296
404721 9856648 Minus 173763-174294
404756 7706327 Plus 82849-83627
404802 4581357 Minus 30093-30600
404984 6939882 Plus 87221-87505
405159 9966252 Plus 79659-79804
405258 7329310 Plus 129930-130076
405288 6139075 Minus 126268-126436
45 405353 2811095 Plus 118525-118892
405362 2337862 Minus 105008-105142,105980-106091,140445-140556,142519-142641
405558 1621110 Plus 4502-4644,5983-6083
405588 5002511 Plus 46180-46366
405605 5836195 Minus 117070-117270
S 0 405701 4263751 Plus 93243-93364
405741 9966947 Minus 156747-156875,156936-157208
405747 8469069 Minus 153933-154060
405771 7018349 Plus 91191-91254,91510-91589
405808 9929207 Plus 109758-111166
5 405684 6758747 Plus 62383-62583
405915 7712162 Minus 43717-43859
406028 8312303 Minus 177469-177829
406085 9123888 Plus 18665-18843
406169 6684220 Minus 12620-14251
406267 7528342 Minus 2570-2731
406326 9212385 Plus 84508-84655
406347 9255981 Plus 90900-91091
406474 9795567 Plus 52758-53211
406577 7711730 Plus 11377-11509
65 406610 8312226 Plus 13096-13334
TABLE 10A: ABOUT 582 GENES SIGNIFICANTLY DOWN-REGULATED IN GLIOBLASTOMA
COMPARED TO NORMAL ADULT CNS TISSUES
Table 10A lists about 582 genes significantly down-regulated in glioblastoma
compared to normal adult CNS tissues. These were selected from 59680 probesets
on the

AffymeUixIEos Hu03 GeneChip array such that the ratio of'average' normal CNS
to'average' glioblastoma was greater than or equal to 3. The'average' normal
CNS level was set
to the 75th percentile amongst various normal CNS tissues. The'average'
glioblastoma level was set to the 85th percentile amongst various tumor
samples. In order to remove
gene-specific background Levels of non-specific hybridization, the 10th
percentile value amongst various non-malignant tissues was subtracted from
both the numerator and the
denominator before the ratio was evaluated.
Pkey: Unique Eos probeset identifier number
75 E%ACCn: Exemplar Accession number, Genbank accession number
UnigenelD: Unigene number
Unigene Title: Unigene gene title
R1: Ratio of 75th percentile normal central nervous system tissue to 85th
percentile tumor
80 Pkey EXACCn UnigenelD Unigene Title Ri
453655 AW960427 Hs.79059 transforming growth factor, beta recepto 136.7
417275 X63578 Hs.295449 parvalbumin 29.0
430829 AW451999 Hs.194024 ESTs 25.7
189


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
410657AF063228Hs.65248dynein,cytoplasmic.intertnediate22.6
polype


419954D14720Hs.93883myelin protein zero 21.2
(Charcot-Marie-Tooth


459247N46243Hs.t ESTs, Highly similar 18.5
10373to T42626 secreted


416133NM Hs.89512ATPase, Ca+transporting,15.5
001683 plasma membra


416018AW138239Hs.78977proprotein convertase 15.2
subtilisinlkexin t


417167AW206437Hs.4290ESTs 14.8


433940H05129Hs.7459cyclic AMP-regulated 13.4
phosphoprotein, 21


413324V00571Hs.75294corticotropin releasing13.1
hormone


439830AA846666Hs.151489ESTs, Weakly similar 12.6
to XE7_HUMAN PROTEI


408068AW148652Hs.167398ESTs 12.6


412636NM Hs.74316desmoplakin (DPI, DPII)12.5
004415


429096A8011106Hs.196012KIAA0534 protein 12.2


412636AA910199Hs.203838ESTs 12.2


423690AA329648Hs.23804ESTs, Weakly similar 12.1
to PN0099 son3 prot


456844AI264155Hs.152981CDP-0iacylglycerol 11.9
synthase (phosphafida


418318U47732Hs.84072transmembrane 4 superfamily10.9
member 3


442593839804Hs.31961ESTs 10.8


446353A1290919Hs.i53661ESTs 10.4


420290AW977318Hs.194480ESTs 10.3


414220BE298094 gb:601118231Fi NIH_MGC_i710.3
Homo Sapiens c


414290AI568801Hs.71721ESTs 10.2


426365AA376667Hs.10263RNA binding motif protein10.0
8B


414937838698Hs.12382ESTs 10.0


419643F06066Hs.91791chromosome 11 open 9.5
reading frame 25


407173T64349 gb:yc10dO8.s1 Stratagene9.5
lung (937210) H


412454855745Hs.167330ESTs 9.5


439366AF100143Hs.6540fibroblast growth (actor9.4
13


415315Ft2240Hs.250655prothymosin, alpha 9.3
(gene sequence 28)


441790AW294909Hs.132208ESTs 9.2


448117H49129Hs.172982ESTs 9.1


400661 9.0


433558AA833757Hs.201769ESTs, Weakly similar 9.0
to T24435 hypotheG


412453820205Hs.167330ESTs 9.0


408920AL120071Hs.48998fibronectin leucine 8.9
rich transmembrane
p


409031AA376836Hs.76728ESTs 8.7


428106BE620016Hs.182470PTD010 protein 8.3


446544AI631932Hs.7047ESTs, Weakly similar 8.2
to Unknown [H.sapie


423479NM Hs.129208death-associated protein8.2
014326 kinase 2


439480AL038511Hs.125316ESTs, Weakly similar 8.2
to S33990 finger pr


418036237976Hs.83337latent transforming 8.0
growth factor beta
b


456490U83171Hs.97203small inducible cytokine8.0
subfamily A (Cy


410200AA082557Hs.101915Stargardt disease 3 8.0
(autosomal dominant)


414602AW630088Hs.76550Homo Sapiens mRNA; 8.0
cDNA DKFZp564B1264
(f


408428NM Hs.44896DnaJ (Hsp40) homolog, 7.9
014787 subfamily B, membe


437073AI885608Hs.94122ESTs 7.9


408434AW195317Hs.107716hypothetical protein 7.9
FLJ22344


438150AA037534Hs.79059transforming growth 7.9
factor, beta recepto


440209H05049Hs.22269neurexin 3 7.8


408119W26213Hs.101672ESTs, Weakly similar 7.8
to T00331 hypothefi


417421AL138201Hs.82120nuclear receptor subfamily7.8
4, group A, m


410587AA370706Hs.86412chromosome 9 open reading7.8
frame 5


429611AI889077Hs.211388Homo Sapiens BAC clone7.7
CTB-60N22 from 7q


405800 7.7


421750AK000768Hs.107872hypothetrcal protein 7.7
FLJ20761


426356BE536836Hs.98682hypothetical protein 7.7
FKSG32


423440825234Hs.143434contactin 1 7.7


445148AI214510Hs.146304ESTs 7.6


416294D86980Hs.79170KIAA0227 protein 7.6


424087N69333Hs.143434contacfin 1 7.6


437479861866Hs.101277ESTs 7.5


405071 7.5


421224AW402154Hs.125812ESTs 7.4


442025AW887434Hs.11810CDA11 protein 7.4


459476BE185844 gb:ILS-HT0731-110500-087-c087.2
HT0731 Homo


430573AA744550Hs.136345ESTs 7.1


401836 7.1


448958AB020651Hs.22653KIAA0844 protein 7.1


430152AB001325Hs.234642aquaporin 3 7.1


419474AW968619Hs.155849ESTs 7.1


401780 7.1


446052AA358760 gb:EST67699 Fetal lung7.0
II Homo Sapiens c


423605AF047826Hs.129887cadherin l9,type 2 7.0


433098AW190593Hs.151143ESTs 7.0


449511AI436187Hs.296261guanine nucleotide 6.9
binding protein (G
pr


451285AW137912Hs.227583Homo Sapiens chromosome6.8
X map Xp11.23 L-


428414AL049980Hs.184216DKFZP564C152 protein 6.8


419273BE271180Hs.293490ESTs, Weakly similar 6.8
to 138022 hypothefi


443155854485Hs.23772ESTs 6.8


450561849674Hs.25909ESTs 6.8


g0 433068NM Hs.288215sialyltransterase 6.8
006456


440729AA904739Hs.128204ESTs 6.8


448426BE018315Hs.280776tankyrase, TRF1-interacting6.7
ankyrin-rela


423589AA328082Hs.209569ESTs 6.6


190


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WO 03/025138 PCT/US02/29560
415681AI379882Hs.72630ESTs 6.5


413510F13044 gb:HSC3HH101 normalized6.4
infant brain cDN


427992Y15014Hs.181353UDP-Gal:betaGIcNAC 6.4
beta 1,3-galactosyitr


453344BE349075Hs.44571ESTs 6.4


450642839773Hs.7130copine IV 6.4


432251AW972983Hs.232165polycythemia rubra 6.4
vera 1: cell surface


429322086984Hs.199243KIAA0231 protein 6.4


444927AW016637Hs.199425ESTs 6.4


447482A8033059Hs.18705KIAA1233 protein 6.4


1 400332S66407Hs.248032FLT4 6.3
~


440703AL137663Hs.7378Homo Sapiens mRNA; 6.3
cDNA DKFZp434G227
(fr


446129AW244073Hs.t45946ESTs 6.3


454076AW204712Hs.61957ESTs 6.3
~


425526AA359933 gb:EST69040 Fetal lung6.3
II Homo Sapiens c


15421913AI934365Hs.109439osteoglycin (osteoinducfive6.3
factor, mime


434273AA913143Hs.26303ESTs 6.2


408480A1350337Hs.164568filuoblast grovrth 6.2
factor 7 (keratinocyte


451301AI769514Hs.209890EST 6.2


430754AW862610Hs.157068ESTs 6.2


438356AA805530Hs.48527ESTs 6.2


422743BE304678Hs.119598ribosomal protein L3 6.2


453355AW295374Hs.31412Homo Sapiens cDNA FLJ114226.2
fis, clone HE


426388AW081394Hs.97103ESTs 6.2


452502A1904296 gb:PM-BT046-220199-286_16.t
BT046 Homo sapi


2 402546 6.1



457534A1761307Hs.232226ESTs 6.1


408165AL137573Hs.43143Homo Sapiens mRNA; 6.1
cDNA DKFZp564A2463
(f


404958 6.1


432501BE546532Hs.25682Homo Sapiens mRNA for 6.1
KIAA1863 protein,


442979AW440782Hs.174743ESTs 6.1


422262AL022315Hs.113987lecfin, galactoside-binding,6.0
soluble, 2


408713NM Hs.47042ectonucleoside triphosphate6.0
001248 diphosphohyd


454065BE394588 gb:601311808Fi NIH 6.0
MGC 44 Homo Sapiens
c


430004027768Hs.227571regulator of G-protein5.9
signalling 4


354o1sz1 s.s


425087862424Hs.126059ESTs 5.9


446298AF187813Hs.i4637kidney-and liver-specific5.9
gene


417761813727Hs.21435ESTs 5.9


424806AA382523Hs.105689MSTP031 protein 5.9


441695T12411Hs.183745hypothetical protein 5.9
FLJ13456


457483AB034694Hs.272558endomucin-1 5.9


417175844558Hs.94002ESTs 5.8


437483AL390174 gb:Homo sapiens mRNA; 5.8
cDNA DKFZp547J184


436427AI344378Hs.143399ESTs 5.8


45411939A1365585Hs.146246ESTs 5.8


459053A1807052Hs.210361ESTs 5.7


411052AW814950 gb:MR1-ST0206-130400-023-d065.7
ST0206 Homo


431063298949Hs.326843hypothetical protein 5.7
bk125H2.1


450382AA397658Hs.60257Homo Sapiens cDNA FLJ135985.7
fis, clone PL


408478NM Hs.45740gamma-aminobutyric 5.7
000806 acid (GAGA) A recepto


442676AI733585Hs.130897ESTs 5.7


446443AV659082Hs.134228ESTs 5.7


400865 5.7


459080AW192083Hs.290855ESTs 5.6


5 407952AI215902Hs.88845ESTs, Highly similar 5.6
5 to T50835 hypothefi


431984AL080239Hs.272284Human DNA sequence 5.6
from clone GS1-256022


425705AF007833Hs.159265kruppel-related zinc 5.6
finger protein hcKr


442238AW135374Hs.270949ESTs, Moderately similar5.6
to F41925 hypot


422994AW891802Hs.296276ESTs 5.6


60457148AF091035Hs.184627KIAA0118 protein 5.6


428356AL046991Hs.10338ESTs 5.6


415927AL120168Hs.78919Kell blood group precursor5.5
(Mcleod pheno


402092 5.5


440526AI832243Hs.211471ESTs 5.5


65444409A1792140Hs.49265ESTs 5.5


417877A1025829Hs.86320ESTs 5.4


458238AW071521Hs.333541beta-amyloid binding 5.4
protein precursor


430702056979Hs.250651H factor 1 (complement)5.4


456189H91010Hs.44940ESTs 5.4


427424AA402453Hs.113011ESTs 5.4


437354AA749215Hs.291886ESTs 5.4


455617BE078070 gb:CM1-BT0614-160300-149-f025.4
BT0614 Homo


429290AF203032Hs.198760neurofilament, heavy 5.3
polypeptide (200kD)


427861AA813185Hs.98183ESTs 5.3


75408556049516Hs.463625-hydroxytryptamine 5.3
(serolonin) receptor


444209AI753134Hs.146494ESTs 5.3


422831802504Hs.332943ESTs 5.3


403180 5.3


418026BE379727Hs.83213fatty acid binding 5.3
protein 4, adipocyle


430339W28608Hs.239625integral membrane protein5.2
2B


431596T34708Hs.272927Sec23 (S. cerevisiae) 5.2
homolog A


431930AB035301Hs.272211cadherin 7, type 2 5.2


437403AI208149Hs.121196ESTs 5.2


191


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
438285AA782845Hs.22790ESTs 5.2


439901N73885Hs.124169ESTs 5.2


438507AA809052Hs.211275ESTs 5.2


449222AW293984Hs.197621ESTs 5.2


402834AK001507Hs.306084Homo Sapiens clone 5.2
FLB6914 PR01821 mRNA,


419042T81429Hs.221065ESTs 5.2


436777AA731199Hs.293130ESTs 5.2


445071A1280246Hs.149504ESTs 5.1


408016AW136827Hs.256096ESTs S.i


1 412047AA934589Hs.49696ESTs 5.1
0


436953AW959074Hs.23648Homo Sapiens cDNA FLJ 5.1
13097 fis, clone NT


436773AW078629Hs.82110PC4 and SFRSi interacting5.1
protein 1


409263AA069573Hs.50319ESTs 5.1


453830AA534296Hs.20953ESTs 5.1


1 459580AA022888Hs.176065ESTs 5.1



417616807728Hs.268668ESTs 5.1


423457F08208Hs.283844similar to rat fricarboxylate5.1
carrier-li


441535AL135735Hs.7885phosphafidylinositol 5.0
binding clathrin as


416490AF090116Hs.79348regulator of Gprotein 5.0
signalling 7


417284N62889Hs.107242Homo Sapiens cDNA FLJ129655.0
fis, clone NT


447135T58148 gb:yb98gO6.s1 Stratagene5.0
lung (937210) H


448605AL109678Hs.21597Homo Sapiens mRNA full5.0
length insert cDN


442240AI791883Hs.292719ESTs 4.9


459399BE407712Hs.i53998crealine kinase, mitochondria)4.9
1 (ubiqui


25427972AA864870Hs.181304putative gene product 4.9


432944AA570687Hs.38512ESTs 4.9


440198BE560093 gb:601345159F1 NIH_MGC_84.9
Homo Sapiens cD


444047A1097452Hs.135095ESTs 4.9


416040AW819158Hs.289044Homo Sapiens cDNA FLJt20484.9
fis, clone HE


444922AI921750Hs.144871Homo Sapiens cDNA FLJ 4.8
13752 fis, clone PL


436670AI690021Hs.201536ESTs 4.8


448072A1459306Hs.24908ESTs 4.8


408936AL138043Hs.293549ESTs 4.8


412622AW664708Hs.171959ESTs 4.8


3 414943D80647Hs.124193ESTs 4.8
S


429254H10133Hs.91846hypothetical protein 4.8
DKFZp761C121


453567AI742835Hs.33368hypotheficalprotein 4.8
FLJ11175


407906AA369665Hs.41185Homo Sapiens mRNA; 4.8
cDNA DKFZp56401262
(f


441028AI333660Hs.17558Homo Sapiens cDNA FLJ 4.7
14446 fis, clone HE


405130 4.7


455225AW996689 gb:OV3-BN0046-150400-151-g094.7
BN0046 Hamo


446218AV657159 gb:AV657159 GLC Homo 4.7
Sapiens cDNA clone


443347A1052543Hs.133244melanoma-derived leucine4.7
zipper, extra-n


402176 4.7


45416577BE063207Hs.79381grancalcin 4.7


436221AK001781Hs.296543Homo Sapiens cDNA FLJ109194.7
fis, clone OV


420480AL137361Hs.98173hypotheficalprotein 4.7


400800Y10262Hs.46925eyes absent (Drosophila)4.6
homotog 3


435161AF124150Hs.272091ESTs 4.6


404793 4.6


430895U66581Hs.248121G protein-coupled receptor4.6
22


438571AW020775Hs.56022ESTs 4.6


445924AI264671Hs.164166ESTs 4,6


444585AW170015Hs.6594ESTs 4.6


55421044AF061871Hs.311736Human DNA sequence 4.6
from clone RP1-238D15


418274AI458587Hs.128677Human DNA sequence 4.6
from clone RP1-50024


425475W56339Hs.107057ESTs 4.6


434311BE543469Hs.266263Homo sapiens cDNA FLJ141154.5
fis, clone MA


414272AI651603Hs.46988ESTs 4.5


445235A1564022Hs.138207ESTs 4.5


414327BE408145Hs.185254ESTs, Weakly similar 4.5
to T24435 hypotheti


414630BE410857 gb:601301 177F1 NIH 4.5
MGC 21 Homo Sapiens
c


414456H74314 gb:yu56e10.r1 Soares 4.5
fetal liver spleen


401024 4.5


65414699A1815523Hs.76930synuclein, alpha (non 4.5
A4 component of am


423449AI497900Hs.33067ESTS 4.5


405138 4.5


413544BE147225 gb:PM2-HT0225-031299-003-f114.5
HT0225 Homo


453880AI803166Hs.28462ESTs, Weakly similar 4.5
to 138022 hypothefi


433521T66087Hs.112482Homo Sapiens unknown 4.4
mRNA sequence


441184AA922009Hs.150269ESTs 4.4


429876A8028977Hs.225974KIAA1054 protein 4.4


445481AW661846Hs.148836ESTs 4.4


452340NM_002202Hs.505ISL1 transcription 4.4
factor, LIMlhomeodoma


75404769 4.4


444331AW193342Hs.24144ESTs 4.4


429726AW628326Hs.27151ESTs 4.4


449093AB035356Hs.22998neurexin 1 4.4


451959AA056203Hs.27337hypothetical protein 4.4
FLJ20623


415716N59294Hs.179662nucleosome assembly 4.4
protein 1-like 1


417888823053 gb:yh31a05.r1 Soares 4.4
placenta Nb2HP Homo


419656AB002314Hs.92025KIAA0316 gene product 4.4


425864U5(i420Hs.159903olfactory receptor, 4.4
family 5, subfamily


192


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
435078AW518888Hs.40937ESTs 4.4


413493BE144444 gb:MRO-HT0168-141199-002-1094.3
HT0168 Homo


432712AB016247Hs.288031sterol-CS-desaturase 4.3
(fungal ERG3, delta


459650825754Hs.301185ESTs 4.3


404828 4.3


423782AI472209Hs.323117ESTs 4.3


426867AA460967Hs.22668ESTs 4.3


426802AA385182Hs.46699ESTs 4.3


457353X65633Hs.248144melanocortin 2 receptor4.3
(adrenocorficotr


1 412112BE180342 gb:RC3HT0622-130400-012-a074.3
~ HT0622 Homo


401522N47812Hs.306198CGI-35 protein 4.3


419055A1365384Hs.11571Homo Sapiens cDNA FLJ115704.3
fis, clone HE


410171H07892Hs.12431ESTs 4.3


419564U08989Hs.91139solute carrier family 4.3
1 (neuronaUepithe


I 458789AL157468Hs.325825Homo Sapiens cDNA FW208484.3
S fis, clone AD


455040AW852286 gb:OVO-CT0225-10040187-0OS4.3
CT0225 Homo


438533AI440266Hs.170673ESTs, Weakly similar 4.3
to T24832 hypothefi


459005AA447679Hs.144558ESTs, Weakly similar 4.2
to ALU1 HUMAN ALU
S


418489U76421Hs.85302adenosine deaminase, 4.2
RNA-specific, 81 (h


433389AF038171 gb:Homo Sapiens clone 4.2
23671 mRNA sequenc


454356AW390363Hs.11522hypothefical protein 4.2
from Xq28


442339BE299668Hs.227591ESTs, Weakly similar 4.2
to 1901303A Leu zip


421249AA285362 gb:HTH277 HTCDL1 Homo 4.2
Sapiens cDNA 5'13'


443998AI620661Hs.296276ESTs 4.2


25 452197AW023595Hs.232048ESTs 4.2


451117AA015752Hs.205173ESTs 4.2


404501AW247252Hs.75514nucleoside phosphorylase4.2


410378823324Hs.41693DnaJ (Hsp40) homolog, 4.2
subfamily B, membe


422528AB011182Hs.118087KIAA0610 protein 4.2


3~ 440323AA970614Hs.127992ESTs 4.1


425767AF054176Hs.159483chromosome 1 open reading4.1
frame 7


434460AA478486Hs.3852KIAA0368 protein 4.1


410362H0481 Hs.93164proprolein convertase 4.1
t subtilisinlkexin t


413121T96090Hs.142678ESTs 4.1


3 409403AA668224Hs.6634Homo Sapiens cDNA: 4.1
FLJ22547 fis, clone
H


450235AA007512Hs.17538ESTs 4.1


449754H00820Hs.30977ESTs, Weakly similar 4.1
to 834087 hypothefi


421813BE048255 gb:1z49b05.y1 NCI CGAP_Bm524.1
Homo sapien


408496AI683802Hs.136182ESTs 4.1


430261AA305127Hs.237225hypothetical protein 4.1
HT023


434101AA625205Hs.259599KIAA1622 protein 4.1


451837T92157Hs.16970ESTs 4.1


411772BE170301 gb:OV4-HT0536-040500-193_f054.1
HT0536 Homo


437630A1252782Hs.153026SWAP-70 protein 4.1


45 430212AA469153 gb:nc67f04.s1 NCI_CGAP_Pr14.0
Homo Sapiens


400216 4.0


429830AI537278Hs.225841DKFZP434D193 protein 4.0


453165574727Hs.32042aspartoacylase (aminoacylase4.0
2, Canavan


418047837633Hs.4847ESTs 4.0


405354 4.0


427931AW206512Hs.186996ESTs 4.0


428775AA434579Hs.i43691ESTs 4.0


449422AA001373Hs.59821ESTs 4.0


453864AW021407Hs.21068hypothetical protein 4.0


5 456407AW968614 gb:EST380690 MAGE resequences,4.0
5 MAGJ Homo


441869NM Hs.8004hunfingfin-associated 4.0
003947 protein interacfin


420784T65158Hs.102399ESTs, Moderately similar4.0
to S65657 alpha


425195AA352026Hs.94319VPS10 domain receptor 4.0
protein


429628H09604Hs.13268ESTs 4.0


410087F12079Hs.332579ESTs 4.0


409840AW502122 gb:Ul-HF-BROp-ajr~-08-0-ULr14.0
NIH_MGC_5


452854AA437061Hs.14060prokineficin 1 precursor4.0


419910AA662913Hs.190173ESTs, Weakly similar 4.0
to A46010 X-linked


427443AA402713Hs.97872ESTs 4.0


65 414990C17758Hs.221652Homo Sapiens cDNA FLJ143233.9
fis, clone PL


412678AA115575Hs.114914ESTs 3.9


405629 3.9


420299A1056871Hs.15276ESTs 3.9


453098225935Hs.86379ESTs 3.9


435752AF230801 gb:Homo Sapiens growth3.9
hormone receptor


441005141305Hs.303172Homo Sapiens mRNA; 3.9
cDNA DKFZp547G133
(fr


414516AI307802Hs.135560ESTs, Weakly similar 3.9
to T43458 hypotheti


442257AW503B31Hs.323370Human EST clone 25267 3.9
mariner lransposon


422563BE299342Hs.19348hypothetical protein 3.9
FLJ13119


75 406697M21388Hs.123017Human unproducfively 3.9
rearranged Ig mu-ch


443850AW014723Hs.334612ESTs 3.9


412677AW029608H5.17384ESTs 3.9


422788AL717352Hs.120828Human ONA sequence 3.9
from clone RPS-876810


405377 3.9


414376BE393856Hs.66915ESTs. Weakly similar 3.9
to 16.7Kd protein
~


453341AI758912Hs.296341adenylyl cyclase-associated3.9
protein 2


431960AW24182tHs.301927c6.lA 3.9


416854H40164Hs.80296Purkinje cell protein 3.9
4


193


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
427264AA400117Hs.125747ESTs 3.9


422746NM Hs.119651glypican 3 3.9
004484


452346BE243534 gb:TCBAP1D0885 Pediatric3.9
pre-B cell acut


414666NM Hs.76828glypican 5 3.8
004466


418217AI910647Hs.13442ESTs 3.8


419118AA234223Hs.139204ESTs 3.8


445017A1205493Hs.176860ESTs 3.8


405867 3.8


4227608E409561 gb:601299865F1 NIH 3.8
21 Homo Sapiens c
MGC


453863X02544Hs.572_ 3.8
_
orosomucoid 1


457821H47166Hs.124322ESTs, Weakly similar 3.8
to A47582 Bell gr


457330A8013818Hs.247220peroxisome biogenesis 3.8
factor 10


435600AL047034Hs.119747ESTs 3.8


456083U46922Hs.77252fragile histidine triad3.8
gene


I 413341H78472Hs.i91325ESTs, Weakly similar 3.8
S to 718967 hypotheti


449057A8037784Hs.22941KIAA1363 protein 3.8


421835F06504Hs.27384ESTs. Moderately similar3.8
to ALU4_HUMAN A


414764AW013887Hs.72047ESTs 3.8


404391 3.7


433629813140Hs.13359ESTs 3.7


424738A1963740Hs.46826ESTs 3.7


401315 3.7


407706AA191085Hs.26612ESTs, Moderately similar3.7
to S23650 retro


440530AA888646Hs.174187ESTs 3.7


25 433930AA620338Hs.273781ESTs 3.7


409662AW452320Hs.279726ESTs 3.7


437268AI754847Hs.227571regulator of G-protein3.7
signalling 4


445668AI248205Hs.153244ESTs 3.7


408593819566Hs.197617ESTs 3.7


3 417091AA193283Hs.291990ESTs 3.7
0


448556AW885606H5.5064ESTs 3.7


423135N67655Hs.26411ESTs 3.7


400135 3.7


459150BE155356 gb:PMt-HT0350-160300-009-d063.7
HT0350 Homo


35 457221AW383197Hs.218260ESTs 3.7


451660AI807927Hs.249601ESTs 3,7


401600BE247275Hs.151787U5 snRNP-specific protein,3.7
116 kD


446818AI342668Hs.279765ESTs 3.7


447795AW295151Hs.i63612ESTs 3.7


4~ 427562856424Hs.26534ESTs 3.6


412258AA376768Hs.324841hypothetical protein 3.6
FLJ22622


454339AW381980 gb:OV4-HT0316-091199-028-d053.6
HT0316 Homo


439274AF086092Hs.48372ESTs 3.6


452381H23329Hs.290880ESTs, Weakly similar 3.6
to ALU1
HUMAN ALU S


45 422897AA679784Hs.4290_ 3.6
ESTs


429656X05608Hs.211584neurofilamenL light 3.6
polypeptide (68kD)


421908AW935200Hs.285814sprouly (Drosophila) 3.6
homolog 4


407978AW385129Hs.41717phosphodiesterase 1A, 3.6
calmodulin-depende


426452AW614271Hs.121647ESTs, Highly similar 3.6
to AC006014 8 simil


400685 3.6


417154AI674701Hs.21388ESTs 3.6


447176242549Hs.160893ESTs 3.6


423893AL031709Hs.134846Human DNA sequence 3.6
from clone 316612
on


449231BE410360Hs.298573KIAA1720 protein 3.6


5 411607AW853498 gb:RCt-CT0252-170200-025-h023.6
5 CT0252 Homo


405977 3.6


441470BE503874Hs.301986ESTs 3.6


423568NM Hs.129818growth arrest-specfic 3.6
005256 2


441235AI884586Hs.135570Homo Sapiens cDNA: 3.6
FLJ21268 fis, clone
C


60 450236AW162998Hs.24684KIAA1376 protein 3.6


425364AF052150Hs.155959Homo Sapiens clone 3.6
24533 mRNA sequence


426775AA384564Hs.108829ESTs 3.6


414831M31158Hs.77439protein kinase, CAMP-dependent,3.6
regulato


416876AW501916Hs.i17897ESTs 3.6


65 400878 3.6


425153AW023193Hs.27046ESTs 3.6


432222AI204995 gb:an03c03.x1 SUatagene3.5
schizo brain St


415047F13142 gb:HSC3JD031 normalized3.5
infant brain cDN


401532 3.5


446495D60923Hs.153460ESTs 3.5


431325AW026751Hs.5794ESTs, Weakly similar 3.5
to 2109260A B cell


445898AF070623Hs.13423Homo Sapiens clone 3.5
24468 mRNA sequence


455901BE155527 gb:PM1-HT0350-190400-013-b083.5
HT0350 Homo


416421AA134006Hs.79306eukaryolic translation3.5
initiation factor


7 455697BE067952 gb:CMO-870365-061299-122-g093.5
5 870365 Homo


405678 3.5


418207C14685Hs.34772ESTs . 3.5


425383D83407Hs.156007Down syndrome critical3.5
region gene 1-lik


417027AA192306Hs.23926Uiadin 3.5


408367AK~1178Hs.44424homolog of rat orphan 3.5
transporter v7-3


417702809935Hs.191146ESTs 3.5


445687W80382Hs.149297ESTs 3.5


408776AA057365Hs.63356ESTs, Weakly similar 3.5
(0138022 hypolheti


194


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
413164BE068494 gb:MRi-BT0371-050500-009-a123.5
BT0371 Homo


414593BE386764 gb:601273249F1 NIH 3.5
MGC 20 Homo Sapiens
c


453220A8033089Hs.32452Homo Sapiens mRNA 3.5
for KIAA1263 protein,


415621AI648602Hs.55468ESTs 3.5


454437A1248173Hs.191460hypolheficalprotein 3.5
MGC12936


446066A1343931Hs.149383ESTs 3.5


423374AB037770H5.127656KIAA1349 protein 3.5


419347C15944Hs.90005superioroervical ganglia,3.5
neural specifi


418516NM Hs.85701phosphoinosifide-&kinase.3.5
006218 catalytic, al


1 451776W45679Hs.169854hypothefical protein 3.5
~ SP192


432305M62402Hs.274313insulin-like growth 3.5
factor binding prole


456995T89832Hs.170278ESTs 3.5


403323 3.5


425022M95724Hs.154207centromere protein 3.5
C 1


15 439394AA149250Hs.56105ESTs 3.4


433803AI823593Hs.27688ESTs 3.4


450715A1266484Hs.31570ESTs, Weakly similar 3.4
to KIAA1324 protein


411474AW84842 7 gb:IL3-CT0214-150200-07SH103.d
CT0214 Homo


415076NM Hs.77890guanylate cyGase 1, 3.4
000857 soluble, beta 3


20 423826020325Hs.1707cocaine-and amphetamine-regulated3.4
Uans


459495BE544158 gb:601076707F1 NIH_MGC_123.4
Homo Sapiens c


427173BE255017Hs.97540ESTs 3.4


408112AW451982Hs.248613ESTs 3.4


446092N33522Hs.145894ESTs 3.4


25 416868A1656856Hs.292597ESTs 3.4


458234BE551408Hs.127196ESTs 3.4


419555AA244416 gb:nc07d11.s1 NCI 3.4
CGAP Pr1 Homosapiens


414314BE312991 gb:601150275F1 NIH 3.4
MGC_19 Homo Sapiens
c


400425AY004252Hs.287385PR domain containing 3.4
12


30 414366BE549143 gb:601076456F1 NIH_MGC_i23.4
Homo Sapiens c


434053AW445136HS.134946ESTs 3.4


449997A1683052Hs.201577KIAA1829 protein 3.4


433461A1636047Hs.197623ESTs 3.4


428006AA418743Hs.98306KIAA1862 protein 3.4


3 424695058331Hs.151899sarcoglycan, delta 3.4
(35kD dystrophin-asso


443294AI733625Hs.133053ESTs 3.4


428212AW444451Hs.134812ESTs 3.4


457673AA551569Hs.272034hypothetical protein 3.4
PR02822


446390AA233393Hs.14992hypothefical protein 3.3
FLJt1151


428536AI143139Hs.2288visinin-like 1 3.3


426597AA382250Hs.145601ESTs 3.3


410366A1267589Hs.302689hypothe6calprotein 3.3


458258AW406546H5.127971ESTs 3.3


401738 3.3


45 409038T97490Hs.50002small inducible cytokine3.3
subfamily A (Cy


425785T27017Hs.159528Homo Sapiens clone 3.3
24400 mRNA sequence


433328AW298159Hs.23644ESTs, Weakly similar 3.3
to S65824 reverse
t


414541BE293116Hs.76392aldehyde dehydrogenase3.3
1 family, member


434998AW975157Hs.26037ESTs 3.3


456359AI967991Hs.93574homeo box D3 3.3


426527NM Hs.170238sodium channel, voltage-gated,3.3
001037 type I, b


454267AA437199Hs.656cell division cycle 3.3
25C


400302N48056Hs.1915folate hydrolase (prostate-specific3.3
memb


434077AF116659Hs.321151Homo Sapiens PR01412 3.3
mRNA, complete cds


S 436602AI793222Hs.166817ESTs 3.3
5


449204AB000099Hs.23251Down syndrome critical3.3
region gene 4


417935853697Hs.170044ESTs 3.3


423310AA325225Hs.124023Homo Sapiens cDNA 3.3
FLJ14218 fis, clone
NT


436624T64297Hs.5241fatty acid binding 3.3
protein 1, liver


()~453406AI192987Hs.61784hypothefical protein 3.3
FLJ1445t


420164AW339037Hs.24908ESTs 3.3


447826AW779317Hs.258556ESTs 3.3


419875AA853410Hs.93557proenkephalin 3.3


444612AW138111Hs.22902ESTs 3.3


65 416504BE159718Hs.85335Homo Sapiens mRNA; 3.2
cDNA DKFZp564D1462
(f


415242845986Hs.295014ESTs 3.2


418188AW139413Hs.151880ESTs 3.2


430355NM Hs.239818phosphoinosifide-3-kinase,3.2
006219 catalyfic, be


421640AW966652 gb:EST378726 MAGE 3.2
resequences, MAGI
Homo


70 432359AA076049Hs.274415Homo Sapiens cDNA 3.2
FLJ 10229 fis, clone
HE


408806AW847814Hs.289005Homo Sapiens cDNA: 3.2
FLJ21532 fis, clone
C


400409AF153341Hs.283954Homo Sapiens winged 3.2
helix/forkhead Uans


446015T30968Hs.13531hypotheficatprotein 3.2
FLJ10971


425495AA358454Hs.78026ESTs, Weakly similar 3.2
to similar to ankyr


75 403092 3.2


452971A1873878Hs.91789ESTs 3.2


454186BE141030 gb:MRO-HT0067-201099-002-h113.2
HT0067 Homo


401485 3.2


401949 3.2


457452AW972675 gb:EST384766 MAGE 3.2
resequences. MAGL
Homo


454100AI693231Hs.126043chromosome 21 open 3.2
reading frame 51


448440AA173467Hs.62402p211Cdc42/Rac1-activated3.2
kinase 1 (yeast


421200AA284811Hs.264433ESTs 3.2


195


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
430142NM Hs.234392platelet-activating 3.2
000437 (actor acetylhydrola


433197AB040889Hs.281022KIAAi456 protein 3.2


443509AV645470 gb:AV645470 GLC Homo 3.2
Sapiens cDNA clone


440827AI733110Hs.t28t28ESTs 3.2


432799NM Hs.278960alpha-1,4-N-acetylglucosaminylVansferas3.2
016161


409257AW370362 gb:RC1-BT0255-181099-012-d073.2
BT0255 Homo


459235BE246010Hs.271468Homo Sapiens mRNA for 3.2
FLJ00038 protein,


416789AA223439Hs.79933cyclin I 3.2


429809AL162010Hs.223603Homo Sapiens mRNA; 3.2
cDNA DKFZp761 D09121
(


1 420156AW449258Hs.6t87ESTs 3.2
~


455577BE006341 gb:RC2-BNOt27-240300-011-b053.2
8N0127 Homo


400617AFi51064Hs.36069hypotheticalprotein 3.2


437129AL049327Hs.302057Homo sapiens mRNA; 3.2
cDNA DKFZp564E016
(fr


451820AW05B357Hs.337353ESTs 3.2


15 457535AA609685Hs.278672membrane component, 3.2
chromosome t1, surfa


419956ALt37939Hs.40096ESTs 3.1


456235AA203637 gb:zx58bi2.ri Soaves 3.i
fetal_liver_spleen_


423930AA332697Hs.42721ESTs 3.1


403796 3.1


414085AA1140t6Hs.75746aldehyde dehydrogenase3.1
1 family, member


445886AI793176Hs.145596ESTs 3.1


414401A1760159Hs.124833ESTs 3.1


441573BE563966Hs.6529ESTs, Weakly similar 3.1
to 178885 serinefth


450725R7t389Hs.175951ESTs 3.1


2 458805A1282933Hs.23294hypotheUCalprotein 3.1
FLJ14393


417868Al078534Hs.122592ESTs 3.1


458391A1792628Hs.133273ESTs 3.1


423346A1267677Hs.t27416synaptojanin 1 3.1


454486AW857077 gb:RC1-CT0302-140300-016-f043.1
CT0302 Homo


408341AW182952Hs.249957ESTs 3.1


410669AW805749Hs.318885superoxide dismutase 3.1
2, mitochondria)


404907 3.1


434910AI333863Hs.215474ESTs, Moderately similar3.i
to altemativel


436990AI149729Hs.120557ESTs 3.1


3 441921A1733376Hs.164478hypothetical protein 3.
S FLJ21939 similar to t


454673AW8i2807 gb:RC3-ST0186-070100-Ot6~043.1
ST0186 Homo


429470AI878901Hs.203862guanine nucleotide 3.1
binding protein (G
pr


404345AA730407Hs.159156protocadherin 11 3.1


408217AI433201Hs.279860tumor protein, translationally-conVolle3.1


417313AA195602 gb:zr32(09.r1 Soaves 3.1
NhHMPu_St Homosapi


427322AK002017Hs.176227hypotheticalprotein 3.1
FLJ11155


411003AA181018Hs.13056hypothetical protein 3.1
FLJ13920


425339AA936330Hs.198113ESTs 3.i


426716NM Hs.171921sema domain, immunoglobulin3.1
006379 domain (1g),


45 449078AK001256Hs.22975KIAA1576 protein 3.1


429608U49250Hs.210862T-box,brain,l 3.1


442308AA989402Hs.111fibroblast growth factor3.1
9 (glia-activat


428465AW970976Hs.293653ESTs 3.1


411666AF106564Hs.71346neurofilament 3 (150kD3.1
medium)


447965AW292577Hs.94445ESTs 3.t


413918AW015898Hs.71245ESTs 3.1


419682H13139Hs.922B2paired-like homeodomain3.1
Uanscription fa


425810AI923627Hs.31903ESTs 3.i


427865AA4t6931Hs.126065ESTs 3.1


55 429060AW139t55Hs.194995hypothetical protein 3.1
DKFZp43400320


430708U78308Hs.278485olfactory receptor, 3.1
family 1, subfamily


448084AI467800Hs.271000ESTs. Weakly 'similar 3.1
to 138022 hypothe6


454506AW847346 gb:RCO-CT0205-240999-021~0t3.1
CT0205 Homo


414629AA345824Hs.76688carboxylesterase 1(monocytelmacrophage3.0


422963M79141Hs.13234ESTs 3.0


417696BE24t624Hs.82401CD69 antigen (p60, 3.0
early Tcell activati


448175BE296174Hs.225160hypothetical protein 3.0
FlJ 13102


414686BE409757Hs.23189ESTs, Moderately similar3.0
to TBB2-HUMAN T


458360A1027207Hs.132253ESTs 3.0


65 451829AW964081Hs.247377ESTs 3.0


445179AI949743Hs.224768ESTs 3.0


433090A1720050Hs.145362immortalization-upregulated3.0
protein


432018AA524447Hs.152377ESTs 3.0


407988N47760Hs.285107hypolheticalprolein 3.0
FLJ13397


405911 3.0


418808A1821836Hs.t0359ESTs 3.0


431900AW972048Hs.192534ESTs 3.0


452893HtBOi7Hs.22869ESTs, Moderately similar3.0
to KIAA1395 pro


423952AW877787Hs.136t02KIAA0853protein 3.0


75 412000AW576555Hs.15780ATP-binding cassette, 3.0
sub-family A (ABC1


405793 3.0


410711AB002316Hs.65746KIAA0318 protein 3.0


411279AW884776 gb:OV4-OT0067-010300-121-d013.0
OT0067 Homo


423957AW978309Hs.136235Homo Sapiens cDNA FLJ135423.0
fis, clone PL


427071AA397958Hs.192719ESTs 3.0


434961AW974956 gb:EST387061 MAGE resequences,3.0
MAGN Homo


TABLE 10B:
196


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
J Pkey CAT Number Accession
409257 1112994_1 AW370362AW809101
409840 1156071 1 AW502122 AW502125 AW50t663 AW501720
411052 1230374 1 AWBt4950 898513 H69459 BE176242 H54583
411279 1237516 1 AW884776 AW935737 AW835261 AW835247 AW835246 AW835263
AW835240 AW835258
411474 1247047_2 AW848427 AW848890 AW848159 AW848118 AW848634 AW848285
AW848086 AW848485 AW848283 AW848162
4t 1607 1251251 1 AW853498 AW853442 AW853590 AW853433 AW853592
411772 12573861 BE170301AW861539AW904851BE1543368E1540908E154275
412112 1277883_1 BE180342 BE180347 AW90t900 BE180222 BE180218 BE180226
BEt80413 BE180416 AW901899 BE180228 AW901897 BE180224 AW901898
BE180223 BE180219 BE180346 BE180343 8E180418 BE180225 BE180221 BE18034t
AW90t894 BE180217 BE180227AW90189i BE180345
1 S AW893614 AW893615 H85799 H83501 BE180220
413164 1351422_1 BE068494 BE068414 BE068332 BE068347 BE068706 BE068623
BE068450 BE068480 BE068350 BE068295 BE068498 BE068765 BE068328
BE068778 BE068671 BE068526 BE068493 BE068433 BE06B740 BE068306 BE068631
BE068580 BE068445 BE068567 BE068521 BE068549
BE068392 BE068307 BE068692 BE068473 BE068754 BE068476 BE068685 BE068626
BE068591 BE068745 BE068434 BE068759 BE068628
BE068723 BE068529 BE068689 BE068383 BE068422 BE068470 BE068522 BE068618
BE068354 BE068748 BE068683 BE068303 BE068602
BE068739 BE068374 BE068302 BE068625 BE068596 BE068663 BE068429 BE068605
BE068693 BE068672 BE068401 BE068579 BE068329
BE068390 BE068419 BE068393 BE068447 BE068675 BE0683i1 BE068540 BE068301
BE068543 BE068719 BE068369 BE068324 BE068588
BE068568 BE068317 BE068384 BE068547 BE068674 BE068436 BE068321 BE068361
BE068676 BE068499 BE068299 BE068352 BE068410
BE068293 BE068418 BE068552 BE068598 BE068327 BE068550 BE068712 BE068661
BE068733 BE068525 BE068752 BE068357 BE068330
BE068565 BE068538 BE068340 BE068537 BE068761 BE068632 BE068758
2S 413493 13735551 BEt444448E144430
413510 1374377_1 F13044 T77009 BE145525 BE145493
413544 1375671 1 BE147225 BE147205 BEi47234
414220 1426940 1 BE298094 BE267860
414314 1435028 1 BE312991 BE272945
414366 1438636 1 BE549143 BE390613 BE277344
414456 1447655_1 H74314 BE299593
414593 1464909 1 BE386764 BE387560
414630 1468083 t BE410857 BE390605
415047 1517450 1 F13t42 242926 F06135 F06147 H08517 D51360 T75341
3 S 417313 166644 1 AA195602 WO1148 N40632
417888 1706092 t 823053 879884 876271
419555 185884 1 AA244416 AA244401
421249 200649 1 AA285362 AW752386 AW847156 AA285373 AW879575 AW879558
421640 204833 1 AW966652 AW966653 AA294989 AA385977
421813 207654 t BE048255 AA313083 AA298419
422760 221034 1 BE409561 BE162756 AW732798
425526 252776 1 AA359933 AA358889 AW955306 AW962995 AW837746 AW837755 AW837697
430212 314437 t AA469153 AI718503 AA469225
432222 343347 1 A1204995 AW827539 AW969908 AW440776 AA528756
4S 433389 36497 1 AF038171 243209 F07347
434961 396357 1 AW974956 AA781075 AA654944
435752 41050 1 AF230801 AF230800AA401795 AA398260
437483 43756 1 AL390174 AW898817
440198 48824 -2 BE560093
S ~ 443509 57199 t AV645470 T84636 T82805
446052 65988 1 AA358760 AA158850 AW062737 AW062738 AV656291
446218 66686 1 AV657159 BE145509 BE145512 BE145505 BE145507
447135 70963 1 T58148 AW516579 AW059603
452346 912206 1 BE243534 BE243752 AI880228 L44326
S S 452502 919733_1 A1904296 BE007223 830687
454065 998401 1 BE394588 AWOZ4754 BE183166 BE183t67
454186 1049791 1
BE141030BE14t474BEt41467BE141753BE141024BE14t761AW177583AW177579AW177582AW17758
5AW177587AW807582AW177581
BEi41477 BE141520 BEi41456 BE141492 BE141028 BE141775 BE141489 BE141751
AW177599 BE141750AW177597 BE14t512 BE141460
BE141749 AWi 77598
454339 1122972 1 AW381980 BE152244 BEi52235 BEt52238 BE152232
454486 1215703 1 AW857077 AW861268 AW847383 AW795787
454506 1219857 1 AW847346 AW847395 AW847408 AW847385 AW847342 AW847396
AW847339 AW801718 AW801787
454673 12286691 AW8t2807AW812815AW812802
455040 1250028 t AW852286 AW851934 AW852096 AW852274
6S 455225 1262318 1 AW996689 AW996380 AW996453 BE085650 AW868687 BE085595
455577 1333898 1 BE006341 BE006307 BE006311
455617 1346117 t BE078070 BE06t030 BE077927
455697 1351148 1 BE067952 BE067945 BE067942 BE067943 BE067949 BE067954
BE067944 BE067953 BE067956 BE067946

455901 1381569 1 BE155527 BE155503 BE155188 BEt55126
70 456235 168686 t AA203637 AA832266 H67452
456407 184986_1 AW968614 AA2d3209 AA281411
457452 339381 1 AW972675 AA541366 AA523039
459150 919196 1 BE155356 BE153488 BE153461 BE155059 BE155210 BE155413 BE153577
8E153688 BE155063 BE155347 AI903640 BE155492
7S TABLE 10C:
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank
Identifier (GI) numbers. 'Dunham, et al.' refers to the publication entitled
'The DNA
sequence of human chromosome 22' Dunham, et al. (1999) Nature 402:489-495.
Strand: Indicates ONA strand from which exons were predicted.
Nt~osifion: Indicates nucleotide posifions of predicted exons.
Pkey Ref SVand Nt~osifion
400661 8118474 Plus 84912-85187
197


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
4006858118768Minus72969-73050,73713-73600


4008651945037Minus44482-45526


4008789864757Plus 31493-32842


4010248117489Plus 60551-60802


4013159212516Minus198960-199619


4014857341723Plus 68009-68209,68841-69077


4015217705251Plus 9127-9234


4015327798785Plus 124414-124950,125050-125418


4017382982169Minus41547-41757


1 4017807249190Minus28397-28617,28920-29045,29135-29296,29411-29567,29705-
29787,30224-30573
~


4018367534063Plus 71981-72084


4019493492889Plus 160728-161660


4020927249154Minus107533-108094


4021767543687Minus10-750


1 4025467637348Plus 24673-25170



4030928954241Plus 174720-175016,175104-175406,175508-175813


4031807523976Minus63603-63759


4033238348082Minus120366-120845


4037968099896Minus75073-77664


4043913135305Minus26030-26173,27852-27997


4047698099713Minus175801-176823


4047937232206Minus61087-61590


4048286580415Minus26291-27253


4049077331453Minus102880-103828


Z 4049587407941Minus2731-0531
5


4050717708797Minus111f5-11552


4051308516045Plus 15023r150449


4051388576241Plus 90303-90516


4053542642452Plus 52213-53089


4053775649375Plus 216656-216848


4056294508116Minus101678-101866


4056784079670Plus 151821-152027


4057931405887Minus89197-89453


4058002791346Plus 19271-19813


3 4058676758731Minus74553-75173
5


4059116758795Plus 101008-101643


4059778247789Minus135548-136177


4O TABLE 11A: ABOUT 533 CNS-ENRICHED GENES SIGNIFICANTLY DOWN-REGULATED IN
GLIOBLASTOMA COMPARED TO NORMAL ADULT CNS TISSUES
Table 11A lists about 533 CNS-enriched genes significantly down-regulated in
glioblastoma compared to normal adult CNS tissues. These were selected from
59680 probesets on
the AtTymetrixlEos Hu03 GeneChip array such that the ratio of 'average' normal
CNS to'average' glioblastoma was greater than or equal to 2. The'average'
normal CNS level was
set to the 75th percentile amongst various normal CNS tissues. The'average'
glioblastoma level was set to the BSth percentile artwngst various tumor
samples. To enrich for CNS
45 specific genes, the ratio of'average' CNS to'average' non-CNS normal adult
tissues was calculated to be greater than or equal to 2. The'average' CNS
level was set to the BSth
percentile amongst vrious CNS tissues. The'average' normal non-CNS adult
tissue level was set to fhe 85th percentile amongst various non-CNS normal
tissues. In order to
remove gene-specific background levels of non-specific hybridization, the 10th
percentile value amongst various non-malignant tissues was subtracted from
both the numerator and
the denominator before the ratios were evaluated.
Pkey: Unique Eos probesel identifier number
ExAccn: ExempIarACCession number, Genbank accession number
UnigenelD: Unigene number
Unigene Title: Unigene gene title
Rt: Ratio of 75th percentile normal central nervous system tissue to 85th
percentile tumor
R2: Ratio of 85th percentile central nervous system tissue to 85th percentile
normal body tissue
55 Pkey ExAccnUnigenelDUnigeneTitle R1 R2


417275X63578Hs.295449parvalbumin 29.0 30.0


430829AW451999Hs.194024ESTs 25.7 6.2


410657AF063228Hs.65248dynein, cytoplasmic, 22.6 25.8
intermediate polype


419954014720Hs.93883myelin protein zero 21 30
(Charcot-Marie-Tooth 2 3


416133NM Hs.89512ATPase, Ca++transporting,. .
001683 plasma membra 15.5 16.8


416018AW138239Hs,78977proprotein convertase 15.2 18.0
subtilisinlkexin t


417167AW206437Hs,4290ESTs 14.8 17.7


433940H05129Hs.7459cyclic AMP-regulated 13.4 18.1
phosphoprotein, 21


413324V00571Hs.75294crorticotropin releasing13.1 18.0
65 hormone


439830AA846666Hs.t51489ESTs, Weakly similar 12.6 16.5
to XE7_HUMAN PROTEI


408068AW148652Hs.167398ESTs 12.6 16.9


429096AB011106Hs.196012KIAA0534 protein 12.2 21.1


412638AA910199Hs.203838ESTs 12.2 16.0


442593839804Hs.31961ESTs 10 15
8 0


446353A1290919Hs.153661ESTs . .
10.4 13.2


426365AA376667Hs.10283RNA binding motif protein10.0 5.9
BB


414937838698Hs.12382ESTs 10.0 10.8


419643F06066Hs.91791chromosome t t open 9.5 10.9
reading frame 25


412454855745Hs.167330ESTs 9 14
5 1


75 439366AF100143Hs.6540fibrobtast growth factor. .
13 9.4 12.3


441790AW294909Hs.132208ESTs 9.2 3.2


448117H49129Hs.t72982ESTs 9.1 12.8


433558AA833757Hs.201769ESTs, Weakly similar 9.0 14.7
to T24435 hypotheti


412453820205Hs.167330ESTs 9 7
0 13


8~ 408920AL120071Hs.48998fibronectin leucine . .
rich transmembrane 8.9 17.3
p


409031AA376836Hs.76728ESTs g,7 g.6


446544AI631932Hs.7047ESTs, Weakly similar 8.2 20.0
to Unknown [H.sapie


439480AL038511Hs.125316ESTs. Weakly similar 8.2 8.3
to 533990 finger pr


198


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
410200AA082557Hs.101915Stargardt disease 3 8.0 8.9
(autosomal dominant)


408428NM Hs.44896DnaJ (Hsp40) homolog, 7.9 9.6
014787 subfamily 8, membe


437073AI885608Hs.94122ESTs 7.9 11.3


408434AW195317Hs.107716hypothetical protein 7.9 16.4
FLJ22344


440209H05049Hs.22269neurexin 3 7.8 34.3


408119W26213Hs.101672ESTs, Weakly similar 7.8 9.0
to T00331 hypothefi


429611AI889077HS.211388Homo Sapiens BAC clone7.7 5.0
CTB-60N22 from 7q


423440825234Hs.143434contactin 1 7.7 9.9


445148AI214510Hs.146304ESTs 7.6 9.1


416294D86980Hs.79170KIAA0227 protein 7.6 7.6


424087N69333Hs.143434contacfin 1 7.6 10.3


437479861866Hs.101277ESTs 7.5 9.3


430573AA744550Hs.136345ESTs 7.1 2.8


448958A8020651Hs.22653KIAA0844 protein 7.1 10.4


419474AW968619Hs.155849ESTs 7.1 3.0


423605AF047826Hs.129887cadherin 19, type 2 7.0 6.9


433D98AW190593Hs.151143ESTs 7.0 9.2


449511AI436187Hs.296261guanine nucleofide 6.9 3.1
binding protein (G
pr


428414AL049980Hs.i84216DKFZP564C152protein 6.8 5.0


443155854485Hs.23772ESTs 6.8 3.5


450561849674Hs.25909ESTs 6.8 8.1


433068NM Hs.288215sialyllransferase 6.8 2.0
006456


423589AA328082Hs.209569ESTs 6.6 10.5


415681A1379882Hs.72630ESTs 6.5 9.0


z5413510F13044 gb:HSC3HH1D1 normalized6.4 7.1
infant brain cDN


427992Y15014Hs.181353UDP-Gal:belaGIcNAc 6.4 9.5
beta t,3-galactosyltr


450642839773Hs.7130copine IV 6.4 5.7


429322D86984Hs.199243KIAA0231 protein 6.4 8.2


447482AB033059Hs.18705KIAA1233 protein 6.4 2.3


446129AW244073Hs.145946ESTs 6.3 8.3


421913A1934365Hs.109439osteoglycin (osteoinductive6.3 2.1
(actor, mime


434273AA913143Hs.26303ESTs 6.2 10.3


408480A1350337Hs.164568fibroblast growth factor6.2 3.5
7 (kerafinocyte


451301AI769514Hs.209890EST 6.2 12.4


35438356AA805530Hs.48527ESTs 6.2 8.1


426388AW081394Hs.97103ESTs 6.2 8.6


452502AI904296- gb:PM-BT046-220199-2866.1 2.8
1 BT046 Homo sapi


408165AL137573Hs.43143Homo sapiens mRNA; 6.1 6.3
cDNA DKFZp564A2463
((


442979AW440782Hs.174743ESTs 6.1 6.3


40408713NM Hs.47042ectonucleoside biphosphate6.0 3.8
001248 diphosphohyd


430004U27768Hs.227571regulator of Gprotein 5.9 21.4
signalling 4


425087862424Hs.126059ESTs 5.9 8.1


441695T12411Hs.183745hypothetical protein 5.9 3.1
FLJ13456


417175844558Hs.94002ESTs 5.8 12.5


45437483AL390174 gb:Homo Sapiens mRNA; 5.8 2.2
cDNA DKFZp547J184


436427A1344378Hs.i43399ESTs 5.8 13.8


450382AA397658Hs.60257Homo Sapiens cDNA FLJ 5.7 4.4
13598 fis, clone PL


408478NM Hs.45740gamma-aminobutyric 5.7 12.5
000806 acid (GAGA) A recepto


442676AI733585Hs.130897ESTs 5.7 6.8


446443AV659082Hs.134228ESTs 5.7 6.4


459080AW192083Hs.290855ESTs 5.6 15.6


431984AL080239Hs.272284Human DNA sequence 5.6 8.2
from clone GSi-256022


428356AL046991Hs.10338ESTs 5.6 6.2


417877A1025829Hs.86320ESTs 5.4 4.9


429290AF203032Hs.198760neurofilamenl, heavy 5.3 13.1
S polypeptide (200kD)


408556U49516Hs.463625-hydroxytryptamine 5.3 6.6
(serotonin) receptor


431930AB035301Hs.272211cadherin 7, type 2 5.2 6.0


438285AA782845Hs.22790ESTs 5.2 7.3


439901N73885Hs.124169ESTs 5.2 2.7


449222AW293984Hs.197621ESTs 5.2 8.1


408016AWi36827Hs.256096ESTs 5.1 2.5


436953AW959074Hs.23648Homo Sapiens cDNA FLJ130975.1 3.0
fis, clone NT


436773AW078629Hs.82110PC4 and SFRSt interacting5.1 7.3
protein 1


409263AA069573Hs.50319ESTs 5.1 12.9


453830AA534296Hs.20953ESTs 5.1 3.4


441535AL135735Hs.7885phosphafidylinositol 5.0 4.8
binding clathrin as


416490AF090116Hs.79348regulator of G-protein5.0 20.1
signalling 7


417284N62889Hs.107242Homo Sapiens cDNA FLJ129655.0 3.9
fis, clone NT


448605AL109678Hs.21597Homo Sapiens mRNA full5.0 6.1
length insert cDN


442240AI791883Hs.292719ESTs 4.9 6.7


427972AA864870Hs.181304putative gene product 4.9 5.2


416040AW819158Hs.289044Homo Sapiens cDNA FLJ 4.9 2.8
12048 fis, clone HE


444922AI921750Hs.144871Homo Sapiens cDNA FLJ137524.8 3.7
fis, clone PL


408936AL138043Hs.293549ESTs 4.8 6.6


75414943D80647Hs.124193ESTs 4.8 3.1


429254H10133Hs.91846hypotheficalprotein 4.8 2.3
DKFZp761C121


407906AA369665Hs.41185Homo Sapiens mRNA; 4.8 9.1
cDNA DKFZp56401262
(f


416577BE063207Hs.79381grancalcin 4.7 2.2


420480AL137361Hs.98173hypothetical protein 4.7 2.8


404793 4.6 2.2


430895U66581Hs.248121G protein-coupled receptor4.6 7.4
22


438571AW020775Hs.56022ESTs 4.6 5.4


444585AW170015Hs.6594ESTs 4.6 6.0


199


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
414272AI651603Hs.46988ESTs 4.5 2.2


414699A1815523Hs.76930synuclein, alpha (non 4.5 30.9
A4 component of am


423449AI497900Hs.33067ESTs 4.5 20.8


433521T66087Hs.112482Homo Sapiens unknown 4.4 2.0
mRNA sequence


429876A8028977Hs.225974KIAA1054 protein 4.4 19.2


429726AW628326Hs.27151ESTs 4.4 10.2


449093AB035356Hs.22998neurexin 1 4.4 9.4


415716N59294Hs.179662nucleosome assembly 4.4 15.1
protein 1-like 1


419656A8002314Hs.92025KIAA0316 gene product 4.4 8.2


425864U56420Hs.159903olfactory receptor, 4.4 2.4
family 5, subfamily


435078AW518888Hs.40937ESTs 4.4 5.7


432712A8016247Hs.28803tsterol-CS-desalurase 4.3 5.9
(fungal ERG3, delta


426867AA460967Hs.22668ESTs 4.3 6.0


412112BE180342 gb:RC3-HT0622-130400-012-a074.3 3.2
HT0622 Homo


410171H07892Hs.1243tESTs 4.3 5.3


442339BE299668Hs.227591ESTs, Weakly similar 4.2 5.0
to 1901303A Leu zip


421249AA285362 gb:HTH277 HTCDLi Homo 4.2 3.5
Sapiens cDNA 5'!3'


422528AB011182Hs.118087KIAA0610 protein 4.2 3.9


434460AA478486Hs.3852KIAA0368 protein 4.1 8.3


410362H04811Hs.93164proprotein convertase 4.1 7.0
subGlisinlkexin t


449754H00820Hs.30977ESTs, Weakly similar 4.1 3.9
to 834087 hypotheti


408496AI683802Hs.136182ESTs 4.1 4.7


434101AA625205Hs.259599KIAA1622 protein 4.1 6.3


430212AA469153 gb:nc67f04.s1 NCI_CGAP4.0 2.5
Pr1 Homosapiens


453165S74727Hs.32042aspartoacylase (aminoacylase4.0 7.4
2, Canavan


456407AW968614 gb:EST380690 MAGE msequences,4.0 5.1
MAGJ Homo


441869NM Hs.8004huntingtin-associated 4.0 32.3
003947 protein interactin


429628H09604Hs.13268ESTs 4.0 4.5


410087F12079Hs.332579ESTs 4.0 6.9


419910AA662913Hs.190173ESTs, Weakly similar 4.0 2.6
to A46010 X-linked


441005241305Hs.303172Homo Sapiens mRNA; 3.9 21.7
cDNA DKFZp547G133
(fr


412677AW029608Hs.17384ESTs 3.9 2.2


453341AI758912Hs.29634tadenylyl cyclase-associated3.9 7.2
, protein 2


416854H40164Hs.80296Purkinje cell protein 3.9 2.2
4


414666NM Hs.76828glypican5 3.8 6.2
004466


418217AI910647Hs.13442ESTs 3.8 3.2


421855F06504Hs.27384ESTs, Moderately similar3.8 2.2
to ALU4_HUMAN A


414764AW013887Hs.72047ESTs 3.8 10.7


433629813140Hs.13359ESTs 3.7 2.7


424738A1963740Hs.46826ESTs 3.7 2.1


407706AA191085Hs.26612ESTs, Moderately similar3.7 5.3
to S23650 reUO


437268AI754847Hs.227571regulator of Gprolein 3.7 53.7
signalling 4


423135N67655Hs.26411ESTs 3.7 21.7


446818AI342668Hs.279765ESTs 3.7 2.6


427562856424Hs.26534ESTs 3.6 3.6


439274AF086092Hs.48372ESTs 3.6 34.5


452381H23329Hs.290880ESTs, Weakly similar 3.6 6.0
to ALU1 HUMAN ALU
S


422897AA679784Hs.4290ESTs 3.6 5.1


429656X05608Hs.211584neurofilament, light 3.6 24.6
polypeptide (68kD}


417154AI674701Hs.21388ESTs 3.6 5.8


447176242549Hs.160893ESTs 3.6 6.4


405977 3.6 3.9


423568NM Hs.129818growth arrest-specific3.6 2.5
005256 2


441235AI884586Hs.135570Homo sapiens cDNA: 3.6 5.4
FLJ21268 fis, clone
C


SS 426775AA384564Hs.108829ESTs 3.6 3.4


414831M31158Hs.77439protein kinase, CAMP-dependent,3.6 2.8
regulato


425153AW023193Hs.27046ESTs 3.6 4.9


446495D60923Hs.1534b0ESTs 3.5 9.8


445898AF070623Hs.13423Homo Sapiens clone 3.5 16.6
24468 mRNA sequence


416421AA134006Hs.79306eukaryotic Uanslation 3.5 5.0
initiation factor


418207C14685Hs.34772ESTs 3.5 16.0


425383D83407Hs.156007Down syndrome critical3.5 6.2
region gene t-lik


417027AA192306Hs.23926Uiadin 3.5 2.5


408367AK001178Hs.44424homolog of rat orphan 3.5 5.3
Uansporter v7-3


408776AA057365Hs.63356ESTs, Weakly similar 3.5 5.5
to 138022 hypotheti


453220AB033089Hs.32452Homo Sapiens mRNA for 3.5 23.6
KIAA1263 protein,


419347C15944Hs.90005superiorcervical ganglia,3.5 42.3
neural specifi


433803AI823593Hs.27688ESTs 3.4 3.6


450715A1266484Hs.31570ESTs, Weakly similar 3.4 4.1
to KIAA1324 protein


415076NM Hs.77890guanylate cyclase t, 3.4 9.8
000857 soluble, beta 3


423826U20325Hs.1707cocaine- and amphetamine-regulated3.4 4.7
traps


427173BE255017Hs.97540ESTs 3.4 2.4


446092N33522Hs.145894ESTs 3.4 3.5


416868A1656856Hs.292597ESTs 3.4 4.5


458234BE551408Hs.127196ESTs 3.4 4.5


434053AW445136Hs.134946ESTs 3.4 3.9


428536AI143139Hs.2288visinin-like 1 3.3 42.3


410366AI267589Hs.302689hypotheticalprotein 3.3 14.4


425785T27017Hs.159528Homo Sapiens clone 3.3 4.6
24400 mRNA sequence


g0 434998AW975157Hs.26037ESTs 3.3 4.7


456359AI967991Hs.93574homeo box D3 3.3 4.4


426527NM Hs.170238sodium channel, voltage-gated,3.3 5.2
001037 type I, b


400302N48056Hs.1915folate hydrolase (prostate-specific3.3 9.0
memb


200


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WO 03/025138 PCT/US02/29560
419875AA853410Hs.93557proenkephalin 3.3 3.6


444612AW138111Hs.22902ESTs 3.3 3.0


415242845986Hs.295014ESTs 3.2 2.2


421640AW966652 gb:EST378726 MAGE resequences,3.2 3.8
MAGI Homo


408806AW847814Hs.289005Homo Sapiens cDNA: 3.2 2.4
FLJ21532 fis, clone
C


446015T30968Hs.13531hypothetical protein 3.2 3.2
FLJ 10971


425495AA358454Hs.78026ESTs, Weakly similar 3.2 2.2
to similar to ankyr


403092 3.2 2.9


452971AI873878Hs.91789ESTs 3.2 4.5


454100A1693231Hs.126043chromosome 21 open 3.2 2.7
reading frame 5t


448440AA173467Hs.62402p211Cdc42IRaci-acfivated3.2 2.8
kinase 1 (yeast


421200AA284811Hs.264433ESTs 3.2 2.7


440827AI733110Hs.128128ESTs 3.2 2.1


429809AL162010Hs.223603Homo Sapiens mRNA; 3.2 4.3
cDNA DKFZp761009121
(


420156AW449258Hs.6187ESTs 3.2 19.0


457535AA609685Hs.278672membrane component 3.2 2.0
chromosome 11, surfs


419956ALi37939Hs.40096ESTs 3.1 8.7


423930AA332697Hs.42721ESTs 3.1 2.7


417868A1078534Hs.122592ESTs 3.1 12.6


423346AI267677Hs.127416synaplojanin 1 3.1 12.0


441921AI733376Hs.164478hypothefical protein 3. t 4.3
FU21939 similar to


429470AI878901Hs.203862guanine nucleofide 3.1 5.3
binding protein (G
pr


408217AI433201Hs.279860turtar protein, Uanslafionallycontrolle3.1 7.1


427322AK002017Hs.176227hypothetical protein 3,1 6.3
FLJ11155


449078AK001256Hs.22975KIAA1576 protein 3.1 30.1


429608049250Hs.210862T-box, brain, t 3. t 2.2


442308AA989402Hs.111fibroblast growth factor3.1 3.0
9 (glia-acfivat


411666AF106564Hs.71346neurofilament 3 (150kD3.1 10.9
medium)


427865AA416931Hs.126065ESTs 3.t 7.5


430708078308Hs.278485olfactory receptor, 3.1 3.4
family 1, subfamily


451829AW964081Hs.247377ESTs 3.0 6.2


405911 3.0 2.4


418808AI821836Hs.10359ESTs 3.0 6.2


452893H180t7Hs.22869ESTs. Moderately similar3.0 5.1
to KIAA1395 pro


423952AW877787Hs.f36102KIAA0853protein 3.0 2.1


412000AW576555Hs.15780ATP-binding cassette, 3.0 2.1
sub-family A (ABCt


405793 3.0 2.7


410711A8002316Hs.65746KIAA0318 protein 3.0 14.3


427071AA397958Hs.192719ESTs 3.0 2.1


453534NM Hs.33187KIAA0748 gene product 3.0 14.5
014796


413903AA496493Hs.23136ESTs 3.0 2.2


426866002330Hs.172816neuregulin t 3.0 11.3


434945A8033065Hs.4280KIAA1239 protein 3.0 3.5


412639AW961284Hs.296235ESTs 2.9 4.9


453590AF150278Hs.33578KIAA0820 protein 2.9 33.1


414502AL133721Hs.224680ESTs 2.9 2.3


434367AB020700Hs.3830KIAA0893 protein 2.9 23.1


425121A1797511Hs.154679synaptotagminl 2.9 8.1


412494AL133900Hs.792ADP-ribosylafion factor2.9 20.8
domain protein 1


401213 2.9 3.2


401028AW673312Hs.50848hypothefical protein 2.9 3.4
FLJ20331


415191AA190381Hs.120810ESTs 2.9 3.0


449275AW450848Hs.205457periaxin 2.9 5.6


419863AW952691Hs.93485Homo Sapiens mRNA; 2.9 35.0
cDNA DKFZp761 D191
(fr


411421BE272110Hs.21177ESTs 2.9 2.0


430865A1073424Hs.5232HSPC125 protein 2.9 11.4


437486AW952089Hs.5636RAB6A, member RAS oncogene2.9 2.2
family


442357AI458586Hs.135706ESTs 2.9 6.0


408274817315 gb:yg12g11.r1SoaresinfantbrainlNIBH2.9 2.2


444185AW298350Hs.66020ESTs 2.8 5.0


420173AA256151Hs.22999ESTs 2.8 5.1


428358AA993222Hs.101915Stargardt disease 3 2.8 7.0
(aulosomal dominant)


447252890916Hs.12449Homo Sapiens Uansmembrane2.8 4.4
protein HTMPt


440260AI972867Hs.7130copinelV 2.8 10.6


417084H08370Hs.33067ESTs 2.8 8.4


438257AW474419Hs.224794ESTs 2.8 2.8


441934T23939Hs.7344ESTs 2.8 6.2


447885F11528Hs.303172Homo Sapiens mRNA; 2.8 3.5
cDNA DKFZp547G133
(fr


423552AF107028Hs.129783sodium channel, voltage-gated,2.8 3.4
type II,


450940AI744943Hs.143209ESTs, Weakly similar 2.8 14.4
to 138022 hypotheti


410011AB020641Hs.57856PFTAIRE protein kinase2.8 21.7
1


445887AI263105Hs.145597ESTs 2.8 5.1


425494N55540Hs.78026ESTs. Weakly similar 2.8 2.4
to similar to ankyr


438202AW169287Hs.22588ESTs 2.8 11.9


436199838946Hs.127951hypothetical protein 2.8 6.0
FLJ14503


434826AF155661Hs.22265pyruvate dehydrogenase2.8 2.4
phosphatase


415462852692Hs.12698ESTs 2.8 3.4


418070NM Hs.83407glutamate receptor, 2.8 4.5
000844 metabotropic 7


432149AW614326Hs.157022ESTs, Weakly similar 2.8 9.5
to T34549 probable


g0 430371D87466Hs.240112KIAA0276 protein 2.B 7.0


437357AL359559Hs.331666Homo Sapiens mRNA; 2.7 2.5
cDNA DKFZp76202215
(f


415838844336Hs.7093ESTs 2.7 3.6


438675AA813725Hs.213568ESTs 2.7 2.5


201


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419558AW953679 gb:EST365749 MAGE resequences,2.7 3.1
MAGC Homo


446318AI949389Hs.18067ESTs 2.7 4.1


445183A8007877Hs.12385KIAA0417 gene product 2.7 5.3


457012841480Hs.127630ESTs 2.7 19.0


431988AC002302Hs.77202protein kinase C, beta2.7 7.2
1


430223NM Hs.235935nephroblastoma overexpressed2.7 2.8
002514 gene


447932AA837474Hs.20021vesicle-associated 2.7 3.8
membrane protein 1
(s


450214BE439763Hs.227571regulator of G-protein2.7 6.9
signalling 4


434731AA648049Hs.1215i8ESTs 2.7 5.0


428839A1767756Hs.82302Homo Sapiens cDNA FU148142.7 5.2
fis, clone NT


407709AA456135Hs.23023ESTs 2.7 2.5


422420U03398Hs.1524tumor necrosis factor 2.7 3.3
(Iigand) superfami


443305A1050693Hs.133318ESTs 2.7 5.9


435648H24347Hs.27524ESTs 2.7 15.0


I 418407AL044818Hs.84928nuclear transcription 2.7 2.7
S factor Y, beta


436771AW975687Hs.292979ESTs 2.7 6.0


428689NM Hs.189810sulfortranferase family2.7 4.8
014351 4A, member 1


440503NM Hs.7235calcium channel, voltage-dependent,2.7 4.4
006539 gamm


441006AW605267Hs.7627CGI-60 protein 2.7 3.1


410330AW023630Hs.46786ESTs 2.6 29.5


434398AA121098Hs.3838serum-inducible kinase2.6 2.6


438831BE263273Hs.6439synapsin II 2.6 7.8


4166 298492Hs.6975PR01073protein 2.6 3.4


412643AW971239Hs.293982ESTs 2.6 2.2


430456AA314998Hs.241503hypotheficalprotein 2.6 17.9


416498U33632Hs.79351potassium channel, 2.6 2.9
subfamily K, member
1


401421 2.6 2.0


419530X98330Hs.90821ryanodine receptor 2.6 4.2
2 (cardi~)


441817AW969706Hs.293332ESTs 2.6 3.8


439203AA448930Hs.8453KIAA1587 protein 2.6 4.2


426054U12431Hs.166109ELAV (embryonic lethal,2.6 5.1
abnormal vision,


444583AW994403Hs.100861hypothetical protein 2.6 3.7
FLJ14600


417919AI928203Hs.86379ESTs 2.6 3.0


434293NM Ns.3796EphB6 2.6 3.2
004445


431716D89053Hs.2680f2fatty-acid-CoenzymeAligase,long-chain2.6 6.4


443037AW500305Hs.299166syntaxin 7 2.6 2.2


440736D56919Hs.265848myomegalin 2.6 7.1


404648 2.6 3.0


429995AA463571 gb:zx72e09.r1 Soares 2.6 3.5
total fetus Nb2HF8_


436508AW604381Hs.i21121ESTs, Weakly similar 2.6 3.9
to S00755 pleckstri


441190H09073Hs.25046ESTs 2.6 3.1


432278AL137506Hs.274256hypothetical protein 2.6 2.9
FLJ23563


442731AI868167Hs.131044ESTs 2.6 4.1


416836D54745Hs.80247cholecystokinin 2.6 14.9


449071NM Hs.22960breast carcinoma amplified2.5 2.4
005872 sequence 2


436321AA709133Hs.180144ESTs 2.5 2.8


439693AI741816Hs.125897ESTs 2.5 3.6


443212AW269515Hs.102500hypothefical protein 2.5 2.8
FLJ20481


423981AL122104Hs.136664Homo Sapiens mRNA; 2.5 3.8
cDNA DKFZp434A1627
(f


407868NM Hs.40637proline-rich Gla (Gcarboxyglutamic2.5 3.1
000950 acid


443992AW02222Hs.322922ESTs 2.5 27.9
8


444124843097Hs.6818ESTs 2.5 5.3


411379AI816344Hs.12554ESTs, Weakly similar 2.5 38.0
to NPL4 HUMAN NUCLE


440474AI207936Hs.7195gamma-aminobutyric 2.5 3.8
acid (GABA) A recepto


446277AI284218Hs.159204ESTs 2.5 2.2


410111AI620206Hs.189647ESTs 2.5 3.5


445162AB011131Hs.12376piccolo (presynapfic 2.5 4.8
cytomaUix protein)


410718AI920783Hs.191435ESTs 2.5 4.5


417201T60432Hs.269084ESTs, Moderately similar2.5 2.9
to AF0979941 L


420274AW968000Hs.143389ESTs, Weakly similar 2.5 2.8
to T14318 ubiquifin


433496AF064254Hs.49765VLCS-H1 protein 2.5 4.7


437331AL353933Hs.21710hypothetical protein 2.5 3.3
DKFZp761G0313


437368AI471969Hs.182606ESTs 2.5 3.0


441985BE047625Hs.169815ESTs 2.5 3.6


410025BE220489Hs.113592ESTs, Moderately similar2.5 9.2
to 154374 gene


414680AA743331Hs.272572hemoglobin, alpha 2 2.5 3.6


429956AI374651Hs.22542ESTs 2.5 23.9


429028AA443439Hs.48797ESTs 2.5 2.8


438109A1076621Hs.71367ESTs, Moderately similar2.5 3.1
to ALU7 HUMAN A


439780AL109688 ~b:Homo Sapiens mRNA 2.5 2.3
full length insert


440888N45600Hs.326880ESTs 2.5 3.9


445246A1217713Hs.147586ESTs 2.5 2.6


440152A8002376Hs.7006KIAA0378 protein 2.4 23.6


432740AF061034Hs.278898tumor necrosis factor 2.4 2.1
alpha-inducible ce


415122D60708Hs.22245ESTs 2.4 3.9


432298AL118812Hs.274293Homo Sapiens mRNA; 2.4 9.8
cDNA DKFZp76161111
(f


437948AA772920Hs.303527ESTs 2.4 9.8


421360AA297012Hs.103839erythrocyte membrane 2.4 2.8
protein band 4.1-li


427115AW972853Hs.112237ESTs 2.4 2.2


452074BE299035Hs.27747G proteincoupled receptor2.4 10.0
37 (endotheli


436639Di4838Hs.111fibroblast growth factor2.4 3.5
9 (glia-acfival


434520AA205273Hs.177011hypotheficalprotein 2.4 3.1


411529AA430348Hs.317596Homo Sapiens cDNA FLJ 2.4 3.0
12927 fis, clone NT


202


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442272AA988302Hs.129172ESTs 2.4 2.1


422927AW247388Hs.301423calcium binding protein2.4 2.7
1 (calbrain)


444647Ht4718Hs.11506Human clone 23589 mRNA2.4 2.8
sequence


415827H17462Hs.23079ESTs 2.4 15.0


451397AA017432Hs.84529ESTs, Weakly similar 2.4 3.9
to 1202_HUMAN ZINC


445200AA084460Hs.12409somatostafin 2.4 3.7


451062AL110125Hs.25910Homo Sapiens mRNA; 2.4 2.4
cDNA DKFZp564C1416
(t


420328Y19062Hs.96870staufen (Drosophila, 2.4 4.3
RNA-binding protein


432122AA526514 gb:ni60t02.s1 NCI_CGAP2.4 4.3
Ov2 Homo Sapiens


1 444125AI124882Hs.118121ESTs 2.4 3.5
0


430538AB032435Hs.242821differenfiafion-associated2.4 10.8
Na-dependent


457519X69438Hs.3052early growth response 2.4 2.4
4


409371851736Hs.12381ESTs 2.4 2.1


456303AA224872Hs.115088ESTs 2.4 3.2


I 440105AA694010Hs.6932Homo Sapiens clone 2.4 23.4
S 23809 mRNA sequence


400979 2.4 4.1


435296849685Hs.24980ESTs 2.4 6.5


408950AA707814Hs.14945long fatty aryl-CoA 2.4 18.5
synthetase 2 gene


452032BE244005Hs.27610refinoic acid-and interferon-inducible2.4 2.2


20 432098AF252297Hs.91546cytochrome P450 refinoid2.4 2.7
metabolizing pr


408974AW015458Hs.297017ESTs 2.4 2.5


412177123091Hs.73734glycoprolein V (platelet)2.4 2.8


413153N94205 gb:za27a08.r1 Soares 2.4 2.5
fetal liver spleen


417583AA668782Hs.191284ESTs, Weakly similar 2.4 2.6
to ALU1 HUMAN ALU
S


25 452034F12234Hs.75893ankydn 3, node of Ranvier2.3 3.0
(ankyrin G)


424940AA985308Hs.194327ESTs 2.3 6.3


431706A1816086Hs.296341adenylyl cyclase-associated2.3 4.1
protein 2


419125AA642452Hs.130881Bell CLLllymphoma 11A 2.3 2.9
(zinc finger pro


423641ALi37256Hs.130489ATPase, aminophospholipid2.3 8.7
transporter-li


30 436407T88803Hs.271507ESTs, Weakly similar 2.3 3.2
to TIM HUMAN PROBAB


448681AL109781Hs.21754Homo Sapiens mRNA full2.3 5.2
length insert cDN


415669NM Hs.78589serine (or cysteine) 2.3 54.7
005025 proteinase inhibito


410765AI694972Hs.66180nucleosome assembly 2.3 9.1
protein 1-like 2


422386AF105374Hs.115830heparan sulfate (glucosamine)2.3 5.0
3-0-sulfot


35 414828AA156651 gb:z105hO5.r1 Soares_pregnanl2.3 2.4
uferus_NbH


445556AI910241Hs.12887actin-related protein 2.3 8.5
3-beta


426968U07616Hs.173034amphiphysin (Stiff-Mann2.3 26.3
syndrome with br


444562AA186715Hs.336429RIKEN cDNA 9130422N19 2.3 2.5
gene


423420AI571364Hs.128382Homo Sapiens mRNA; 2.3 7.6
cDNA DKFZp76111224
(f


40 439450851613Hs.125304ESTs 2.3 26.3


427127AW802282Hs.22265pyruvate dehydrogenase2.3 2.2
phosphatase


447179AW015633Hs.157299ESTs 2.3 3.8


414711Af310440Hs.288735Homo Sapiens cDNA FLJ135222.3 2.3
fis, clone PL


433449AW772282 gb:hn71b05.x1 NCI CGAP2.3 3.8
Kidl1 Homosapien


45 414320U13616Hs.75893ankyrin 3, node of 2.3 2.5
Ranvier (ankyrin G)


416778M16505Hs.79876steroid suttatase (microsomal),2.3 7.8
arylsulf


425130AA448208Hs.99163ESTs 2.3 4.1


456664AW963354Hs.334409metallothionein 1G 2.3 2.5


438283AI458931Hs.37282ESTs 2.3 4.2


50 417455AW007066Hs.18949ESTs, Weakly similar 2.3 3.0
to CA2B HUMAN COLLA


412100AW892731 gb:CMO-NN0005-100300-279-c022.3 3.7
NN0005 Homo


448981AI968719Hs.195387ESTs 2.3 3.2


416101824854Hs.268806ESTs 2.3 6.5


439731A1953135Hs.45140hypotheficalprotein 2.3 17.8
FLJ14084


55 415734NM Hs.78748KIAA0237 gene product 2.3 40.1
014747


424596AB020639Hs.151017estrogen-related receptor2.3 2.9
gamma


420230AL034344Hs.284186forkhead box C1 2.3 2.4


451559AL119980Hs.20935hypotheficalprotein 2.3 5.7
DKFZp7610221


404835 2.3 2.1


60 456765A1497900Hs.33067ESTs 2.3 4.1


455517AW984068 gb:RCO-HN0006-160300-011-e062.3 2.4
HN0006 Homo


408206AF041853Hs.43670kinesin family member 2.2 18.5
3A


411770NM Hs.71992heat shock protein 2.2 3.9
014278 (hsp110 family)


430105X70297Hs.2540cholinergic receptor, 2.2 2.6
nicotinic, alpha p


65 458694F12832Hs.13298ESTs 2.2 4.9


415091AL044872Hs.779103-hydroxy-3-methylglutaryl-Coenzyme2.2 4.4
A sy


439642W81441Hs.153967ESTs 2.2 2.4


450138AW152104Hs.200879ESTs 2.2 4.9


454222BE144344Hs.7589ESTs, Weakly similar 2.2 3.7
to A46010 X-linked


70 405326 2.2 2.7


431342AW971018Hs.21659ESTs 2.2 5.2


453101AW952776Hs.94943ESTs 2.2 3.3


408897N50204Hs.283709lipopolysaccharide 2.2 2.8
specific response-7
p


451398AI793124Hs.144479ESTs 2.2 4.6


75 438208AL041224Hs.65379ESTs 2.2 10.4


408449NM Hs.166161dynamin 1 2.2 6.1
004408


414130AI670831Hs.71592Homo Sapiens cDNA: 2.2 3.1
FLJ21893 fis, clone
H


445016U79716Hs.i2246reelin 2.2 3.9


424375AF070547Hs.146312Homo Sapiens clone 2.2 2.3
24820 mRNA sequence


g0 424645NM Hs.151449KIAA0535 gene product 2.2 11.7
014682


409729D51315Hs.106289ESTs 2.2 4.9


432809AA565509Hs.131703ESTs 2.2 19.9


422890243784Hs.75893ankyrin 3, node of 2.2 10.4
Ranvier (ankyrin G)


203


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428532AFi57326Hs.184786TBP-interacting protein2.2 6.5


413074A1871368Hs.8417hypothetical protein 2.2 3.4
DKFZp761M0423


414442AA156238Hs.32501ESTs 2.2 3.2


452768AW069459Hs.61539ESTs 2.2 2.0


450440AB024334Hs.25~1tyrosine 3-monooxygenaseltryptophan2.2 3.2
5-mo


426281AK000987Hs.169111oxidation rosistance 2.2 2.3
1


428411AW291464Hs.10338ESTs 2.2 2.3


413787AI352558Hs.75544tyrosine 3-monaoxygenase/tryptophan2.2 3.1
Smo


451734NM Hs.26944neurogranin (protein 2.2 8.5
006176 kinase C substrate,


439108AW163034Hs.6467synaptogyrin 3 2.2 7.9


405385 2.2 2.4


447285A1371849Hs.200696ATPase, Class VI, type2.2 2.2
11C


452667187219Hs.13219ESTs 2.2 3.1


422234AF119818Hs.113287discs, large (Drosophila)2.1 8.3
homolog-associ


1 410339AI916499Hs.298258ESTs 2.1 3.2
5


413231D87461Hs.75244BCL2-like 2 2.1 4.5


447104Rt9085Hs.210706Homo Sapiens cDNA FLJ131822.1 2.2
fis, clone NT


451952AL120173Hs.301663ESTs 2.1 36.5


415841245637Hs.7093ESTs 2.1 2.4


441086A1928489Hs.213490ESTs, Weakly similar 2.1 2.2
to N33 HUMAN N33 PR


450407NM Hs.24969gamma-aminobutyric 2.1 6.6
000810 acid (GAGA) A recepto


427627887582Hs.179915guanine nucleotide 2.1 5.3
binding protein (G
pr


449712856545Hs.6100ESTs 2.1 4.5


409660AW452065Hs.258905ESTs 2.1 2.1


430434AL049548Hs.241420Homo Sapiens mRNA for 2.1 5.4
KIAA1756 protein,


434138AA625804 gb:zu86h01.s1 Soares_testis_NHT2.1 3.0
Homo sap


448610NM Hs.21602net (chicken)-like 2.1 4.8
006157 1


418948AI217097 gb:qd43h07.x1 Soares 2.1 2.9
fetal_hearLNbHHI9W


414876AW950925Hs.924crystallin, mu 2.1 3.4


440426AI159800Hs.7181Homo Sapiens cDNA FLJ136632.1 3.7
fis, clone PL


451249AA016227Hs.27280ESTs 2.1 4.1


451475119093Hs.26450KIAA0725 protein 2.1 2.1


448743AB032962Hs.21896KIAA1136 protein 2.1 29.7


430814U89336Hs.247993NG5 protein 2.1 2.7


426990AL044315Hs.173094Homo Sapiens mRNA for 2.1 2.3
KIAA1750 protein,


426642AW068223Hs.171581ubiquifin Gterminal 2.1 4.5
hydrolase UCH37


427335AA448542Hs.251677G antigen 7B 2.1 2.2


459089F13036Hs.27373Homo Sapiens mRNA; 2. t 2.3
cDNA DKFZp56401763
(f


435832AA425688Hs.41641Bruno (Drosophila) 2.1 5.9
-like 4, RNA binding


446383105816Hs.92511ESTs 2.1 2.9


412768AW996044Hs.26239Human DNA sequence 2.1 2.1
from clone RP11-03882


453976BE463830Hs.163714ESTs 2.1 4.2


415111839039Hs.328455EST 2.1 3.3


452238F01811Hs.187931ESTs 2.1 4.9


445279841900Hs.22245ESTs 2.1 9.8


448799AI937094Hs.179080ESTs ~ 2.1 3.1


418338NM Hs.84154neuronal pentraxin 2.1 8.3
002522 1


445725AK000956Hs.13209hypothetical protein 2.1 5.4
FW10094


443537D13305Hs.203cholecystakinin B receptor2.1 4.1


454066X00356Hs.37058catcitoninlcalcilonin-related2.1 6.4
polypeptid


429954AI918130Hs.21374ESTs 2.1 7.2


415292H29016Hs.200576ESTs 2.1 3.9


423563834734Hs.75209protein kinase (cAMP~ependent,2.1 3.1
catalyti


424906AI566086Hs.153716Homo Sapiens mRNA for 2.1 4.7
Hmob33 protein, 3'


459309AA040620Hs.5672hypothetical protein 2.1 2.2
AF140225


439340AB032436Hs.6535brain-specific Na-dependent2.1 4.7
inorganic ph


402598BE314624Hs.3128polymerase (RNA) II 2.1 5.4
(DNA directed) polyp


435406F26698Hs.4884calciuMcalmodulin-dependent2.1 6.6
protein kin


448792842550Hs.12826ESTs 2.1 4.1


449500AW956345Hs.12926ESTs 2.1 2.4


441134W29092Hs.7678cellular retinoic acid-binding2.1 5.8
protein 1


433361AW469373Hs.300141ribosomal protein L39 2.1 2.7


452946X95425Hs.31092EphAS 2.1 5.0


426167AF039023Hs.167496RAN binding protein 2.0 2.2
6


453666AW015681Hs.135229ESTs, Weakly similar 2.0 3.1
to A2BP_HUMAN ATAXI


424632AB014523Hs.151406KIAA0623 gene product 2.0 3.5


448589AF017090Hs.21554KIAA1107 protein 2.0 4.1


430416AC005531Hs.57806Homo Sapiens PAC clone2.0 2.3
RP4-701016 from 7


445627AW818475Hs.7363ESTs 2.0 2.1


417092H97508Hs.181165eukaryotic translation2.0 2.5
elongation factor


453653AW505554Hs.144559ESTs 2.0 4.7


435850AF250847Hs.283514mitochondria) ceramidase2.0 3.7


435086AW975243Hs.122596ESTs 2.0 2.1


423191D61506Hs.8417hypothetical protein 2.0 2.1
DKFZp761M0423


411562AL050201Hs.70769hypothefical protein 2.0 2.8
DKFZp586E1923


431645AF078849Hs.266483dynein light chain-A 2.0 2.5


429834AI929645Hs.225936synapsin I 2.0 3.6


439607BE540565Hs.159460ESTs 2.0 17.5


408033AW138045Hs.242256ESTs 2.0 4.0


430317AB020645Hs.239189glutaminase 2.0 2.7


419631AW188117Hs.303154popeye protein 3 2.0 2.6


432660A1288430Hs.64004ESTs 2.0 2.3


454048H05626Hs.6921ESTs 2.0 15.9


204


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426917AA913814 Hs.172854 DKFZP586B0923 protein3.1
2.0


423246AL119114 Hs.77196 spectrin, alpha, non-erylhnxyfic2.9
1 (alp 2.0


415989AI267700 Hs.317584 ESTs 2.0 4.8


420276AA290938 Hs.190561 ESTs, Highly similar 5.1
to SORL_HUMAN SORTI 2.0


424983AI742434 Hs.169911 ESTs 2.0 15.9


446296AA985662 Hs.63131 Homo Sapiens cDNA FLJ 2.7
13155 fis, clone NT 2.0


450006AI241555 Hs.60171 ESTs 2.0 3.5


TABLE:
ltB


1 Pkey:Unique Eos probeset identifier number
O


CAT
number:
Gene
cluster
number


Accession:Genbank accession numbers


Pkey CAT Number Accession


I 408274104999 1 Ri 7315 243964 AA053547
S


4121001277224 1 AW892731 H08502 245826


4121121 BE180342 BE180347 AW901900 BE180222 AW901899 BE180228
BE180218 BE180226 BE180413 BE180416 AW901897 BE180224
1277883


_ BE180341 AW901894
AW901898 BE180223 BE180219 BE180346 BE180343BE180217 BE180227
BE180418 BE180225 BE180221 AW901891


BE180345 AW893614 AW893615 H85799 H83501
BE180220


20 4131531350849 1 N94205 BE067565 BE067556


4135101374377 1 F13044 T77009 BE145525 BE145493


414828149563 1 AA156651 AA156622 814472


418948180808 1 AI217097 AW886090 W38035 W38792
AA232835 AW936043


419558185904 1 AW953679 AW953680 AA244436 H82527
AA361046 AA244483 H82526


25 421249200649 1 AA285362 AW752386 AW847156 AA285373
AW879575 AW879558


421640204833 1 AW966652 AW966653 AA294989 AA385977


429995311738 1 AA463571 AI277645 AL118763


430212314437 1 AA469153 A1718503 AA469225


432122341756 1 AA526514 AW973343 AA554293


30 4334493665321 AW772282AA592974


434138380572 1 AA625804 AW418787 AW074833 AI675642
AI393368


43748343756 1 AL390174 AW898817


43978047673 1 AL109688 823665 826578


452502919733 1 A1904296 BE007223 830687


3 4555171321782 1 AW984068 AW984072 AW984077



456407184986_1 AW968614 AA243209 AA281411


TABLE
11C:


Pkey:Unique number corresponding to an Eos
probesel


40 Ref: Sequence souroe. The 7 digit numbers et al.' refers to
in this column are Genbank Identifier the publication
(GI) numbers. 'Dunham, enfitled 'The DNA


sequence of human chromosome 22" Dunham,
et al. (1999) Nature 402:489-495.


Strand:Indicates DNA strand from which exons
were predicted.


Nt~osifion:
Indicates
nucleofide
posifions
of
predicted
exons.


45 Pkey Ref Strand Nl_position


4009798072554 Plus 160842-161028


4012139858408 Plus 98243-98380,98489-98619


4014217452889 Minus 142291-142461


4030928954241 Plus 174720-175016,175104-175406,175508-175813


50 4046489796894 Minus 115334-116020


4047937232206 Minus 61087-61590


4048356970743 Plus 85462-85684,88139-88287,90338-91018,94827-94990


4053264375975 Plus 10633-10709,30805-30893,38078-38253.55112-55327,57718-
57818,66696-66841


4053856552772 Plus 48332-48454


5 4057931405887 Minus 89197-89453
5


4059116758795 Plus 101008-101643


4059778247789 Minus 135548-136177


6O TABLE 12A: ABOUT 678 GENES UP-REGULATED IN LOWER GRADE GLIOBLASTOMA
COMPARED TO NORMAL CENTRAL NERVOUS SYSTEM
a a fists a u1 genes up-regu a a m ower gra a g io astoma compar to morma
centra nervous sys em ese were se ecte om 80 probesets on
the AffymetrixlEos Hu03 GeneChip array such that the ratio of 'average" LGG
to'average' CNS fissues was greater than or equal to 2.5. The "averse' LGG
level was set to the 85°'
percentile amongst various LGG tumors. The'average' normal CNS fissue level
was set to the 85'" percenfile amongst various CNS tissues. In order to remove
gene-specific
background levels of non-specific hybridization, the 10"' percentile value
amongst various non-malignant fissues was subtracted from both the numerator
and the denominator before
6$ the ratio was evaluated.
Pkey: Unique Eos probesel idenfifier number
ExAccn: Exemplar Accession number, Genbank accession number
UnigenelD: Unigene number
Unigene Title: Unigene gene Gtle
70 Rt: Ratio of LOWER GRADE GLIOBIASTOMA to normal CNS
Pkey ExAan UnigenelDUnigene TiBe R1


412420 AL035668Hs.73853bone morphogenetic 20.3
protein 2


424800 AL035588Hs.153203MyoD family inhibitor19.5


75 453392U23752Hs.32964SRY (sex determining 18.5
region Y)-box 11


402604 Target Exon 16.9


444190 A1878918Hs.10526cysteine and glycine-richi5.0
protein 2


409638 AW450420Hs.21335ESTs 14.0


443731 A1083928Hs.145418ESTs 14.0


g0 456759BE259150Hs.127792delta (Drosophila)-like13.6
3


447342 AI199268Hs.19322Homo Sapiens, Similar12.2
to RIKEN cDNA 2010


433001 AF217513Hs.279905clone H00310 PR00310p110.3


427019 AA001732Hs.173233hypothefical protein 9.5
FLJ 10970


205


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
425187AW014486Hs.22509ESTs 9.0


440210AW674562Hs.125296ESTs 8.8


448769N66037Hs.38173ESTs 8.4


437034AA742643 gb:ny9lcOt.s1 NCI_CGAP_GC818.2
Homosapiens


449539W80363Hs.58446ESTs 8.1


417061AI675944Hs.188691Homo Sapiens cDNA 8.0
FLJ12033 fis, clone
HE


435020AW505076Hs.301855DiGeorge syndrome 7,8
crifical region gene
B


414217AI309298Hs.279898Homo Sapiens cDNA: 7.7
FLJ23165 fis, clone
L


449300AI656959Hs.346514ESTs 7.6


449969AW295142Hs.180187Homo Sapiens cDNA 7.5
FLJ14337 fis, clone
PL


452372AI885742Hs.228474ESTs 7.2


410102AW248508Hs.279727ESTs: homologue of 7.2
PEM-3 [Ciona savignyi


417308H60720Hs.81892KIAA0101 gene product7.2


447004AW296968Hs.157539ESTs 7.1


1 418113AI272141Hs.83484SRY (sex determining 7.1
S region Y)-box 4


424635AA420687Hs.115455Homo Sapiens cDNA 7.1
FLJ14259 fis, clone
PL


406478 Target Exon 7.1


428728NM Hs.191381hypothefical protein 6.9
016625


414761AU077228Hs.77256enhancer of zeste 6.9
(Drosophila) homolog
2


428037N47474Hs.89230potassium intertnediatelsmall6.7
conductance


423343AA324643Hs.246106ESTs 6.7


418097845137Hs.21868ESTs 6.7


431553X78075Hs.2799cartilage linking 6.6
protein 1


412326807566Hs.73817small inducible cytokine6.6
A3 (homologous


425397J04088Hs.156346topoisomerase (DNA) 6.4
II alpha (170kD)


419169AW851980Hs.262346ESTs, Weakly similar 6.4
to S72482 hypothe6


431117AF003522Hs.250500delta (Drosophila)-like6.4
1


445908813580Hs.13436Homo Sapiens clone 6.3
24425 mRNA sequence


402855 NM 001839':Homo Sapiens6.2
calponin 3, acid


424009F11690 gb:HSC30D041 normalized6.2
infant brain cDN


400419AF084545 Target 6.2


446584053445Hs.15432downregulated in ovarian6.0
cancer 1


414020NM Hs.75703small inducible cytokine6.0
002984 A4 (homologous


426140AF131798Hs.343768Homo Sapiens clone 5.9
25119 mRNA sequence


427144X95097Hs.2126vasoacfive intesfinal5.9
pepfide receptor
2


416658003272Hs.79432fibrillin 2 (congenital5.8
contracturat ara


405238 Target Exon 5.7


421977W94197Hs.110165ribosomal protein 5.7
L26 homolog


405348 07001664:gi~12698061~dbj~BA821849.1~5.6
(AB


428795845503Hs.97469ESTs, Highly similar 5.4
to A39769 N-acetyll


422672X12784Hs.i collagen, type IV, 5.3
19129 alpha 1


403349NM ephrin-B3 5.3
001406


453941039817Hs.36820Bloom syndrome 5.2


429139F09092Hs.66087ESTs 5.2


454860AW835767 gb:OV4-LT0016-240200-110-b085.2
LT0016 Homo


452279AA286844Hs.61260hypothetical protein 5.1
FLJ13164


418030BE207573Hs.83321neuromedin B 5.1


429469M64590Hs.27 glycine dehydrogenase5.1
(decarboxylafing;


450639AI703186Hs.277174ESTs 5.1


412811H06382 ESTs 5.1


442832AW206560Hs.253569ESTs 5.1


436608AA628980 down syndrome critical5.1
region protein DS


408161AW952912Hs.300383hypothetical protein 5.1
MGC3032


443744A1084326Hs.271548ESTs, Weakly similar 5.1
to 178885 serinetth


447497AW167254Hs.205722ESTs 5.0


450811AI739486Hs.245497ESTs 5.0


433244AB040943Hs.271285KIAA1510 protein 4.9


438458AW975186 gb:EST387294 MAGE 4.9
resequences, MAGN
Homo


438456AA913381Hs.20594ESTs 4.9


411048AK001742Hs.67991hypolheficalprotein 4.9
DKFZp434G0522


456304A1820973 gb:nc21c02.y5 NCI 4.9
CGAP Pr1 Homo Sapiens


442547AA306997Hs.217484ESTs, Weakly similar 4.9
to ALU1 HUMAN ALU
S


419991AJ000098Hs.94210eyes absent (Drosophila)4.8
homolog 1


402274 019000498':gij4567179jgbjAAD23607.1jAC004.8


420092AA814043Hs.88045ESTs 4.8


436282891913Hs.272104ESTs, Moderately similar4.8
to ALU1 HUMAN A


430809AI791150Hs.262009ESTs, Moderately similar4.8
to 138022 hypot


455104BE064863 gb:RC1-BT0313110300-015-f064.8
BT0313 Homo


403961 TargetExon 4.8


424954NM Hs.1846tumor protein p53 4.8
000546 (Li-Fraumeni syndrome)


414825X06370Hs.77432epidermal growth factor4.8
receptor (avian


447891841754Hs.6496ESTs 4.7


423529T87318Hs.120411ESTs 4.7


422737M26939Hs.119571collagen, type III, 4.7
alpha 1 (Ehters-Danl


7 428722076456Hs.190787fissue inhibitor of 4.6
S metalloproteinase
4


437698861837Hs.7990ESTs. Moderately similar4.6
to 184505 calci


403481 Target Exon 4.6


426075AW513691Hs.270149ESTs, Weakly similar 4.6
to 2109260A B cell


422170AI791949Hs.112432anti-Mullerian homwne4.6


g0 416379N38857Hs.203933ESTs 4.6


406481 Target Exon 4.5


456052BE311901Hs.28935gb:601142614F1 NIH 4.5
MGC 14 Homo Sapiens
c


423178A1033140Hs.124983Homo Sapiens mRNA; 4.5
cDNA DKFZp564C142
(fr


206


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
411642NM Hs.71132neuroligin 1 4.5
014932


428282N34905Hs.44653Homo Sapiens cDNA: 4.5
FW22669 fis, clone
H


432625AI243596Hs.94830ESTs, Moderately similar4.5
to T03094 A-kin


452994AW962597Hs.31305KIAA1547 protein 4.5


449961AW265634Hs.133100ESTs 4.4


401454 NM 014226':Horta Sapiens4.4
renal tumor anti


406395 Target Exon 4.4


432281AK001239Hs.274263hypothetical protein 4.4
FU10377


453792ALi34539Hs.254129KIAA1678 4.4


415131D61119 gb:HUM158C11B Gontech4.4
human fetal brain


437695AA769202Hs.192142ESTs 4.4


422081AW136820Hs.196011ESTs 4.4


437748AF234882Hs.5814suppression of tumorigenicity4.3
7


433323AA805132Hs.i59142ESTs 4.3


I 420352BE258835 gb:601117374F1 NIH 4.3
S MGC 16 Homo Sapiens
c


444218AF070641Hs.10684Homo Sapiens clone 4.3
24421 mRNA sequence


441035AI694309Hs.126458ESTs 4.3


443836BE221613Hs.140553ESTs 4.3


425292NM Hs.15554537 kDa leucine-rich 4.3
005824 repeal (L88) protein


450166AA429504 ESTs 4.3


429149AW193360Hs.197962ESTs, Weakly similar 4.2
to 138022 hypothefi


422798892347Hs.34574ESTs. Weakly similar 4.2
to ALUt HUMAN ALU
S


451254AI571016Hs.172967ESTs 4.2


409189AA125984 gb:zn27hO6.ri SUatagene4.2
neuroepithelium


445118AI208762Hs.345572ESTs 4.2


444326A1939357Hs.270710ESTs 4.2


456060C14904Hs.45184Homo Sapiens cDNA 4.2
F1J12284 fis, clone
MA


404120 C500053T:gi~3298595~gb~AAC41376.1~4.2
(AFO


436899AA764852Hs.291567ESTs 4.1


407624AW157431Hs.248941ESTs 4.1


453361AA035197Hs.107375ESTs 4.1


447439AA313565Hs.145020ESTs, Weakly similar 4.1
to KIAA1205 protein


438372AI140189Hs.123191ESTs 4.1


438624AA889055Hs.123468ESTs 4.1


422493AW474183Hs.250173hypothetical protein 4.1
F1J13158


406672AI760903 gb:wi09h08.x1 NCI 4.1
CGAP_CLL1 Horrro
Sapiens


425295AA431366Hs.37251ESTs 4.1


425849AJ000512Hs.296323seromlglucocorficoid 4.1
regulated kinase


434206AW136973Hs.180479ESTs, Weakly similar 4.0
to 569890 mitogen
i


420602AF060877Hs.99236regulator of G-protein4.0
signalling 20


400645 Target Exon 4.0


456306AA225313Hs.222886ESTs, Weakly similar 4.0
to TRHY_HUMAN TRICH


419326W94915Hs.42419ESTs 4.0


414948C15240Hs.182155ESTs 4.0


423198M81933Hs.1634cell division cycle 4.0
25A


411537BE073250 gb:MRO-BT055i-060300-102-e054.0
BT0551 Homo


421637AF035290Hs.106300Homo Sapiens clone 3.9
23556 mRNA sequence


439231AW581935Hs.141480Homo Sapiens mRNA; 3.9
cDNA DKFZp434N079
(fr


429433AA452899Hs.213586ESTs. Weakly similar 3.9
to KIAA1353 protein


424186AI536021Hs.288706Homo Sapiens cDNA 3.9
FLJ10281 fis, clone
HE


449932AI675444Hs.263024ESTs 3.9


434072H70854Hs.283059Homo Sapiens PR01082 3.9
mRNA, complete cds


434784AA649051Hs.164007ESTs 3.9


425146AW954627 gb:EST366697 MAGE 3.9
resequences, MAGC
Homo


428538AA446440Hs.98643ESTs 3.9


443318A1051603Hs.i33141ESTs 3.9


416857AA188775Hs.292453ESTs 3.9


411688AW953440 gb:EST365510 MAGE 3.9
resequences, MAGB
Homo


447343AA256641Hs.236894ESTs, Highly similar 3.9
to S02392 alpha-2-m


425905AB032959Hs.318584novel C3HC4 type Zinc3.8
finger (ring finge


403696 C4001100':gi~5852342~gbIAAD54015.1~3.8
(AFO


415884H22966Hs.13471ESTs 3.8


432646AW753310 gb:RC3CT0254-031099-012-c053.8
CT0254 Homo


447057AI423407Hs.157697ESTs 3.8


400814 Target Exon 3.8


441329AI203575Hs.46821hypothefical protein 3.8
FLJ20086


416664H72780Hs.20289ESTs 3.8


426044AA502490Hs.170290ESTs 3.8


455646BE064420 gb:RC4-BT0311-241199-012-c083.8
BT0311 Homo


419043T19167Hs.89566els variant gene 1 3.8


445075AI651827Hs.344767ESTs 3.8


45721AW972565Hs.32399ESTS, Weakly similar 3.8
1 to 551797 vasodilat


420004AW975532Hs.164039ESTs, Moderately similar3.8
to 138022 hypot


428060AA420616Hs.249483ESTs 3.7


7 416427BE244050Hs.79307RaGCdc42 guanine exchangefactor(GEF)3.7
5


453038AW292415Hs.20509HBV pX associated 3.7
protein-8


404584 Target Exon 3.7


447143AW292408Hs.152290ESTs, Highly similar 3.7
to JC2463 vasoacfiv


453438AI469935Hs.22792ESTs 3.7


g0 429643AA455889Hs.167279FYVE-finger.containing3.7
RabS effector pro


458072AI890347Hs.271923Homo Sapiens cDNA: 3.7
FLJ22785 fis, clone
K


459660M79082 ESTs 3.7


432188A1362952Hs.2928solute comer family 3.7
7 (cafionic amino


207


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
430744AA485229Hs.105649ESTs 3.7


454392BE260893Hs.236131homeodomain-interacting3.7
protein kinase 2


454457AW753456 gb:OV2-CT0261-261099-011-dti3.7
CT0261 Homo


435095AA021160Hs.4750hypothetical protein 3.7
OKFZp564K0822


438206AA780385Hs.187885ESTs 3.7


418967NM Hs.89535bactericidaUpermeability-increasing3.7
001725 pro


427809M26380Hs.180878lipoprotein lipase 3.7


427722AK000123Hs.180479hypotheticalprotein 3.7
FLJ20116


413986243567 gb:HSC1FC021 normalized3.7
infant brain clNl


438898AI819863Hs.106243ESTs 3.7


418483W26076Hs.221847ESTs 3.7


415849820529Hs.6806ESTs 3.6


438380Tt)<430Hs.6194chondroitin sulfate 3.6
proteoglycan BEHABIb


440296D30829Hs.180610splicing factor prolinelglutamine3.6
rich (


1 438025AW501360Hs.258910ESTs 3.6
S


458970AW246119Hs.25300phosphatidylinositol 3.6
4-kinase type II


448002Y15227Hs.20149deleted in lymphocytic3.6
leukemia, 1


432058AW665996Hs.130729ESTs, Weakly similar 3.6
to ALU1 HUMAN ALU
S


409557BE182896Hs.211193ESTs 3.6


418049AA211467Hs.190488Homo Sapiens, Similar 3.6
to nuclear kx;aliz


425331AW962i28 gb:EST374201 MAGE resequences,3.6
MAGG Homo


424051AL110203Hs.138411Homo Sapiens mRNA; 3.6
cDNA DKFZp586J 1922
(f


404185 Target lion 3.6


427517AA644142Hs.7107ESTs, Weakly similar 3.6
to ALU7 HUMAN ALU
S


421094AW978202Hs.289064hypothetical protein 3.6
FLJ22251


440388AI693520Hs.223000ESTs 3.6


415934NM Hs.992phospholipase A2, group3.6
000928 IB (pancreas)


408292AW178363 gb:RC3-HT0105-010999-002-HO63.6
HT0105 Homo


442432BE093589Hs.38178hypothetical protein 3.6
FLJ23468


451826AA020741Hs.171611ESTs 3.6


427375AL035460Hs.177536metallocarboxypeplidase3.6
CPX-1


419485AA489023Hs.99807ESTs, Weakly similar 3.6
to unnamed protein


416370N90470Hs.203697ESTs, Weakly similar 3.6
to 138022 hypotheti


418400BE243026Hs.301989KIAA0246 protein 3.6


3 436674AA725002Hs.272018low molecular mass 3.5
5 ubiquinone-binding
pr


407013035637 gb:Human nebulin mRNA,3.5
partial cds


403108 ENSP00000241415':Hypothetical3.5
67.7 kDa p


422564AI148006Hs.222120ESTs 3.5


450297AW901347Hs.38592hypothetical protein 3.5
FLJ23342


436338W92147Hs.118394ESTs 3.5


447458A1741082Hs.158961ESTs 3.5


457364AW971037 gb:EST383123 MAGE resequences,3.5
MAGK Homo


458814AI498957Hs.170861ESTs, Weakly similar 3.5
to 1195_HUMAN ZINC


441701AW339828Hs.127497ESTs 3.5


405558 Target Exon 3.5


452682AA456193Hs.9071progesterone membrane 3.5
binding protein


434589AF147363 gb:HomosapiensfulllengthinsertcDNA3.5


443282T47764Hs.132917ESTs 3.5


405183 NM 016358':Homo Sapiens3.5
Iroquois homeobo


410064X53416Hs.195464tilamin A, alpha (actin-binding3.5
protein-


425234AW152225Hs.165909ESTs, Weakly similar 3.5
to 138022 hypotheti


404272 Target Exon 3.5


428808AA436007Hs.188780ESTs 3.5


447444AK000318Hs.18616hypothetical protein 3.5
FLJ20311


450475AW805634Hs.205015ESTs 3.4


454451AW846706 gb:OV3-CT0192-211099-008-g023.4
CT0192 Homo


400379NM Homo Sapiens ovarian 3.4
018432 cancer related prot


440948AW188311Hs.128619ESTs 3.4


449611A1970394Hs.197075ESTs 3.4


445666859960Hs.282386ESTs 3.4


445828F05802Hs.81907ESTs 3.4


437528N59646Hs.169745crumbs (Drosophila) 3.4
homolog 1


442927A1024347Hs.131519ESTs 3.4


451130A1762250Hs.345554ESTs 3.4


454765AW819629 gb:RCSST0293-140200-014-H053.4
ST0293 Homo


459200Y09306Hs.30148homeodomain-interacting3.4
protein kinase 3


433791AA719352Hs.112718ESTs 3.4


444911006117Hs.250xanthene dehydrogenase3.4


4397538E262233Hs.7423hypothetical protein 3.4
from EUROIMAGE 2168


440933AI208217Hs.142879ESTs 3.4


447726AL137638Hs.19368matrilin 2 3.4


403849 Target Exon 3.4


422418AK001383Hs.116385hypothetical protein 3.3
FLJ10521


439533W76021 gb:zd64c04.r1 Soares 3.3
fetal heart NbHHI9W


416422H60457 ESTs, Moderately similar3.3
to ZN91 HUMAN Z


441668AI611973Hs.136313ESTs 3.3


432890NM Hs.279751sialic acid binding 3.3
014442 Ig-like lectin 8


412135AW895309 gb:OV4-NN0038-300300-155-e073.3
NN0038 Homo


417130AW276858Hs.81256S100 calcium-binding 3.3
protein A4 (calcium


447854AW138454Hs.11594ESTs 3.3


448048BE281291Hs.170408ESTs, Moderately similar3.3
to A47582 B-cel


404632 NM 022490:Homo Sapiens3.3
hypothetical prot


411565AW851728 gb:MR2-CT0222-011199-007-d063.3
CT0222 Honro


208


CA 02459219 2004-03-17
WO 03/025138 PCT/US02/29560
436267AW450938Hs.t801i5ESTs 3.3


426625T78300Hs.300642serologically defined 3.3
colon cancer anfig


401272 C9000559':gi~12314195~emb~CA899338.t~3.3
(A


433128AB021923Hs.23367EST-YDi protein 3.3


401702 NM 001171':Homo Sapiens3.3
ATP-binding toss


454363AW816274Hs.250154hypothetical protein 3.3
FLJ12973


440332AI218517Hs.188051ESTs 3.3


454177AW807321 gb:MR4-ST0062-240300-003g053.3
ST0062 Homo


423784AK000039Hs.132826Homo Sapiens cDNA FLJ149133.3
fis, clone PL


440688AW404591Hs.147440ESTs, Weakly similar 3.3
to Z192_HUMAN ZINC


410267AW978005Hs.t2600N~thylmaleimide-sensifivefactorattach3.3


455778BE088746 gb:CM2-BT0693-210300-123-4093.3
BT0693 Homo


430183BE010038 gb:PM3-BN0176-100400-001043.2
BN0176 Homo


451597AW295250Hs.207536ESTs 3.2


I 451446AI826288Hs.171637hypothefical protein 3.2
S MGC2628


421353AW292857Hs.255130ESTs 3.2


4427t0A1015631Hs.23210ESTs 3.2


420560AW207748Hs.59115ESTs 3.2


417404NM Hs.82101plecksUin homology-like3.2
007350 domain, family


437834AA769294Hs.283854gb:nz36g03.s1 NCI CGAP3.2
GCB1 Homo Sapiens


430694AA81~24Hs.30936ESTs, Weakly similar 3.2
to H2BH HUMAN HISTO


412021AW885592 gb:RC4-OT007i-090300-011-g113.2
OT0071 Homo


443431A1056847Hs.20654ESTs 3.2


445774A1254165Hs.339968ESTs 3.2


413335A1613318Hs.48442ESTs 3.2


450692H50603Hs.94037hypothefical protein 3.2
FLJ23053


411671BE049094 ESTs 3.2


404592 NM 022739':Homo Sapiens3.2
E3 ubiquifin lig


402747 Target Exon 3.2


428600AW863261Hs.242413hypothefical protein 3.2
DKFZp434K1421


420300AA258245Hs.127573Homo Sapiens FKSG41 3.2
(FKSG41 ) mRNA, compl


445347AF035318Hs.12533Homo Sapiens clone 3.2
23705 mRNA sequence


458438AI141520Hs.t51464ESTs, Weakly similar 3.2
to ALUC_HUMAN !!!!


442314AI311854Hs.129220ESTs 3.2


436291BE568452Hs.344037protein regulatorofcytokinesisl3.2


413249AF167160Hs.75251DEADIH (Asp-Glu-Ala-AspIHis)3.2
box binding


448789BE539108Hs.22051hypothetical protein 3.2
MGC15548


403291 Target Exon 3,2


436210AI825420Hs.197824ESTs 3.2


418079840056Hs.691tESTs 3.2


413951AW051200Hs.75640natriuretic pepfide 3.2
precursor A


435828AA700705Hs.13852ESTs 3.2


437722AW292947Hs.122872ESTs, Weakly similar 3.2
to JU0033 hypotheti


451418BE387790Hs.26369hypothefical protein 3,2
FLJ20287


405046 C3000978:gi~9280045~dbj~8AB01579.1~3.1
(A80


444315807860Hs.20039ESTs 3.1


453096AW294631Hs.11325ESTs 3.1


433835AI806185 gb:wf26at0.x1 Scares 3.1
NFL T GBC Si Homo
s


430608845584Hs.23025ESTs, Weakly similar 3.1
to ALUS_HUMAN ALU
S


453324W26592Hs.232089ESTs 3.1


414884854418Hs.183745hypothetical protein 3.1
FLJ13456


446862AV660697Hs.282700ESTs 3.1


427241AA399988Hs.112087Human DNA sequence 3.1
from clone RP11-530N1


416486H8t336Hs.37560ESTs 3.1


429940W25215 gb:zb87a09.rt Scares 3.1
senescent_fibroblas


430535AW968485 gb:EST380561 MAGE resequences,3.1
MAGJ Homo


439544W26354Hs.28891hypothefical protein 3.1
FLJ11360; artemis
p


437083AW082597Hs.244862ESTs 3.t


435677AA694142Hs.293726ESTs, Weakly similar 3.1
to TSGA RAT TESTIS


458810BE407125Hs.231510ESTs 3.1


443484A1091458Hs.134559ESTs 3.1


427581NM Hs.179703KIAA0129 gene product 3.1
014788


444016AA448154 gb:zw82h09.r1 Scares 3.1
tesfis-NHT Homo sap


423337NM_004655Hs.127337axin 2 (conducfin, 3.1
axil)


403288 C100173T:gi~751 t20i~pirp279043.1
hypothe


450125AA005418Hs.158186ESTs 3.1


438138898299Hs.177502ESTs 3.1


436222A1208737Hs.122810Homo Sapiens cDNA FLJ114893.1
fis, clone HE


443433844743Hs.301667ESTs 3.1


443725AW245680Hs.9701growth arrest and DNA~amage-inducible,3.t


432044AW972727 gb:EST384819 MAGE resequences,3.1
MAGL Homo


405760 Target Exon 3.1


423789AK002084Hs.132851hypolhefical protein 3.1
FLJ11222


411605AW006831Hs.t77530ESTs 3.1


417893AA290605Hs.190002ESTs 3.1


449246AW411209Hs.23363hypothetical protein 3.1
FLJ10983


429528AI985303Hs.99361ESTs 3.1


456645AF227156Hs.110t03RNA polymerise I transcripfion3.1
factor RR


412490AW803564Hs.288850Homo Sapiens cDNA: 3.1
FLJ22528 fis, clone
H


g0 421679AI475110Hs.203933ESTs 3.1


434503T96231Hs.17762ESTs 3.1


450756A1733488Hs.144062ESTs 3.t


415293849462Hs.106541ESTs 3.0


209




DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.
CECI EST LE TOME 1 DE 4
CONTENANT LES PAGES 1 A 211
NOTE : Pour les tomes additionels, veuillez contacter 1e Bureau canadien des
brevets
JUMBO APPLICATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME
THIS IS VOLUME 1 OF 4
CONTAINING PAGES 1 TO 211
NOTE: For additional volumes, please contact the Canadian Patent Office
NOM DU FICHIER / FILE NAME
NOTE POUR LE TOME / VOLUME NOTE:

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Administrative Status

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Administrative Status

Title Date
Forecasted Issue Date Unavailable
(86) PCT Filing Date 2002-09-17
(87) PCT Publication Date 2003-03-27
(85) National Entry 2004-03-17
Examination Requested 2007-09-14
Dead Application 2009-09-17

Abandonment History

Abandonment Date Reason Reinstatement Date
2008-09-17 FAILURE TO PAY APPLICATION MAINTENANCE FEE

Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Application Fee $400.00 2004-03-17
Maintenance Fee - Application - New Act 2 2004-09-17 $100.00 2004-03-17
Registration of a document - section 124 $100.00 2005-03-09
Maintenance Fee - Application - New Act 3 2005-09-19 $100.00 2005-08-31
Registration of a document - section 124 $100.00 2005-09-13
Registration of a document - section 124 $100.00 2006-06-02
Maintenance Fee - Application - New Act 4 2006-09-18 $100.00 2006-09-06
Maintenance Fee - Application - New Act 5 2007-09-17 $200.00 2007-09-05
Request for Examination $800.00 2007-09-14
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
PDL BIOPHARMA, INC.
Past Owners on Record
AFAR, DANIEL
AZIZ, NATASHA
EOS BIOTECHNOLOGY, INC.
GISH, KURT C.
HEVEZI, PETER A.
MACK, DAVID H.
PROTEIN DESIGN LABS, INC.
WILSON, KEITH E.
ZLOTNIK, ALBERT
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Abstract 2004-03-17 1 63
Claims 2004-03-17 3 100
Description 2004-03-17 228 15,191
Description 2004-03-17 213 15,216
Description 2004-03-17 201 15,258
Description 2004-03-17 139 12,073
Cover Page 2004-05-06 1 33
Description 2004-03-18 250 17,855
Description 2004-03-18 300 20,524
Description 2004-03-18 300 16,860
Description 2004-03-18 300 25,705
Description 2004-03-18 77 3,424
Claims 2007-09-26 3 67
Correspondence 2005-06-16 1 21
PCT 2004-03-17 51 3,703
Assignment 2004-03-17 4 139
Correspondence 2004-05-04 1 27
Prosecution-Amendment 2004-03-17 447 26,088
Assignment 2005-03-09 14 366
Assignment 2005-09-13 2 78
Assignment 2006-06-02 3 103
Prosecution-Amendment 2007-09-14 1 40
Prosecution-Amendment 2007-09-26 5 119

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