P53-regulated genes

• US 6,171,798 B1
• Filed: 11/17/1999
• Issued: 01/09/2001
• Est. Priority Date: 03/27/1998
• Status: Expired due to Term

• Current Assignee: Princeton University, Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Princeton University, Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Tom, Edward Yat Wah, Levine, Arnold L., Murphy, Maureen Elizabeth, Gish, Kurt Carlyle, Mack, David H.
• Primary Examiner(s): Schwartzman, Robert A.
• Assistant Examiner(s): Lishibuya, Mark
• Application Number:
  US09/442,039
• Time in Patent Office: 419 Days
• Field of Search: 435/6, 435/325, 435/366, 536/23.1, 536/24.3, 536/24.31, 536/24.33
• US Class Current: 506/9
• CPC Class Codes: C12Q 1/6809 Methods for determination or identification of nucleic acids involving differential detection
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites

Abstract

Many genes are identified as being p53-regulated which were not heretofore known to be p53-regulated. This includes both genes whose expression is induced and genes whose expression is repressed by the expression of wild-type p53. Monitoring expression of these genes is used to provide indications of p53 status in a cell. Such monitoring can also be used to screen for useful anti-cancer therapeutics, as well as for substances which are carcinogenic. Defects in p53 can be bypassed by supplying p53 induced genes to cells. Defects in p53 can also be bypassed by supplying antisense constructs to p53-repressed genes.

Claims

1. A method of diagnosing cancer or determining p53 status in a sample suspected of being neoplastic, comprising the steps of:

comparing the level of expression of an RNA transcript or its translation product in a first sample of a first tissue to the level of expression of the transcript or translation product in a second sample of a second tissue, wherein the first tissue is suspected of being neoplastic and the second tissue is a normal human tissue, wherein the first and second tissue are of the same tissue type, and wherein the transcript is a transcript of a gene selected from the group consisting of IG GAMMA-1 CHAIN C REGION (HUMAN), Human 1 g gamma3 heavy chain disease OMM protein mRNA, 274912 MYELIN TRANSCRIPTION FACTOR 1 (Homo sapiens), 152524 CYCLIN-DEPENDENT KINASE INHIBITOR 1 (Homo sapiens), H. sapiens mRNA for 43 kDa inositol polyphosphate 5-phosphatase, Human N-acetylgalactosamine 6-sulphatase (GALNS) gene, exon 14, 155730 KERATIN, TYPE I CYTOSKELETAL 17 (HUMAN), H. sapiens mRNA (clone

     9112), kinase related protein, Human placental cDNA coding for 5′

nucleotidase (EC3.1.3.5), H. sapiens MLN62 mRNA, Human activated p21cdc42Hs kinase (ack) mRNA, complete cds., 81780 COMPLEMENT C4 PRECURSOR (Homo sapiens), 172486 clone, mRNA for tuberin, or TSC2 gene, Homo sapiens of cardiac alpha-myosin heavy chain gene. KERATIN, TYPE II CYTOSKELETAL 5 (HUMAN);

contains MSR1 repetive element, 182000 FK506-BINDING PROTEIN PRECURSOR (Mus musculus), Human insulin-like growth factor-binding protein-3 gene, complete Cds, clone HL1006d, 72466 ALPHA CRYSTALLIN B CHAIN (HUMAN), Homo sapiens mRNA for serum response factor-related protein, RSRFR2, 198656 HEPATOCYTE GROWTH FACTOR-LIKE PROTEIN PRECURSOR (Homo sapiens), 62461 SMALL NCUELAR RIBONUCLEORPORTEIN Particle N (SNRPN), contains MSR1 repetive element, 155335 INTEGRIN ALPHA-3 (Homo sapiens), 41792 TUBULIN BETA-2-CHAIN (HUMAN), Human estradiol 17 beta-dehydrogenase gene, complete cds, H. sapiens mRNA for cystathionine-beta-synthase, Homo sapiens of cardiac alpha-myosin heavy chain gene, Human mRNA for thyroglobulin, Human guanine nucleotide regulatory protein (ABR) mRNA, complete cds, Human novel growth factor receptor mRNA 3′

Cds, 142899 DNA-DIRECTED RNA POLYMERASE III LARGEST SUBUNIT (Plasmodium falciparum), Human mRNA for collagen VI alpha-1 C-terminal globular domain, Homo sapiens sodium channel type I, beta subunit (SCN1B) mRNA, complete cds., 50887 GUANINE NUCLEOTIDE DISSOCIATION STIMULATOR RALGDSA (Mus musculus), Human cytochrome P450 4F2 (CYP4F2) mRNA, complete cds, Human MAGE-2 gene exons 1-4, complete cds, H. sapiens mRNA for tansforming growth factor alpha, 38251 H sapiens HSJ1 mRNA, p53, H. sapiens mRNA for intestine-specific annexin, KERATIN, TYPE ICYTOSKELETAL 15 (HUMAN);

contains MER20 repetitive element 5065 GROWTH ARREST AND DNA-DAMAGE-INDUCIBLE PROTEIN GADD45 (Homo sapiens), Human steroidogenic acute regulatory protein (StAR) mRNA, complete cds, LYSYL HYDROXYLASE (PLOD), (HUMAN);

151767 FASL RECEPTOR PRECURSOR (Homo sapiens), Homo sapiens creatine transporter mRNA, complete cds, KERATIN TYPE I CYTOSKELETAL 15 (HUMAN);

contains MER20 repetitive element, Human mRNA for thyroperoxidase, 275040 HEPATOCYTE GROWTH FACTOR-LIKE PROTEIN PRECURSOR (HUMAN), 121731 CYTOCHROME P450 IVB1 (Rattus norvegicus), Homo sapiens dopamine transporter (SLC6A3) mRNA, complete cds, 139080 COMPLEMENT DECAY-ACCELERATING FACTOR 1 PRECURSOR (Homo sapiens), H. sapiens mRNA for caveolin, Human endogenoous retrovirus type C onccovirus sequence, 31481 TYROSINE-PROTEIN KINASE HCK (Homo sapiens), Homo sapiens ribosomal protein S6 kinase 2 (RPS6KA2) mRNA, complete cds, Human Fas antigen (fas) mRNA, complete cds, Human mRNA encoding pregastrin (a regulatory hormone of gastric acid secretin and growth of the gastrointestinal mucosa), H. sapiens mRNA for placental growth factor (PIGF), H. sapiens mRNA for placenta growth factor (PIGF), Human PML-2 mRNA, complet Cds, Human mRNA (KIAA0027) for ORF, partial cds, Human placenta-specific growth hormone mRNA, complete cds, Human high conductance inward rectifier potassium channel alpha subunit mRNA, complete cds, Human cytochrome P450 IID6 (CYP2D6) gene, complete cds, 180447 FIBROBLAST GROWTH FACTOR RECEPTOR 3 PRECURSOR (Homo sapiens), 153585 EBNA-2-NUCLEAR PROTEIN (Epstein-barr virus), 36678 TROPONIN C, ISOFORM 2 (Balanus nubilis), 182125 HDL-BINDING PROTEIN, HUMMLC2At;

Homo sapiens;

593 base pairs, 80486 LIVER CARBOXYLESTERASE PRECURSOR (HUMAN), 121916 NEUTRAL CALPONIN, SMOOTH MUSCLE (Sus scrofa), Human 11 beta-hydroxysteroid dehydrogenase type II mRNA, complete cds, Homo sapiens interferon regulatory factor 1 gene, complete cds, Human Fas antigen (fas) mRNA, complete cds, NEUTROPHIL OXIDASE FACTOR (p67 PHOX) (HUMAN), Human 11 kd protein mRNA, complete cds, Human semaphorin V mRNA, complete cds, MYELIN TRANSCRIPTION FACTOR 1 (HUMAN), 175991 NEURONAL CALCIUM SENSOR 1 (Rattus norvegicus), 81422 HUMAN SMOOTH MUSCLE ALPHA-ACTIN (AORTIC TYPE), Human mRNA for irp protein (int-1 related protein), Human Fas antigen (fas) mRNA, complete cds, Human beta-migrating plasminogen activator inhibitor 1 mRNA 3′

end, 26063 COMPLEMENT C4 PRECURSOR (Homo sapiens), 142450 VASCULAR ENDOTHELIAL GROWTH FACTOR PRECURSOR (Rattus norvegicus), Human visinin-like peptide 1 homolog mRNA, complete cds, H. sapiens mRNA for red cell anion exchanger (EPB3, Ae1, Band

     3) 3′

non-coding region, Human laminin S B3 chain (LAMB3) mRNA, complete cds, Human cytochrome P450 IID6 (CYP2D6) gene, complete cds, Human hexokinase 1 (HK1) mRNA, complete cds, Human mRNA for the MDM2 gene, Human mRNA for cytochrome P-450LTBV, RYANODINE RECEPTOR, SKELETAL MUSCLE (HUMAN), 39052 POTASSIUM CHANNEL PROTEIN EAG (Drosophila melanogaster), and 124416 SERINE THREONINE-PROTEIN KINASE COT-1 (Neurospora crassa);

categorizing the first sample as neoplastic or as having a mutant p53 when expression is found to be lower in the first sample than in the second sample.

2. The method of claim 1 wherein a comparison of at least two of the transcripts or translation products is performed.

3. The method of claim 1 wherein a comparison of at least five of the transcripts or translation products is performed.

4. The method of claim 1 wherein a comparison of at least ten of the transcripts or translation products is performed.

5. The method of claim 1 wherein a comparison of at least twenty of the transcripts or translation products is performed.

6. The method of claim 1 wherein a comparison of at least 32 of the transcripts or translation products is performed.

7. The method of claim 1 wherein a comparison of at least fifty of the transcripts or translation products is performed.

8. The method of claim 1 wherein a comparison of 70 of the transcripts or translation products is performed.

9. The method of claim 1 wherein the level of expression of the RNA transcripts is determined using an array of nucleic acid molecules attached to a substrate in predetermined positions.

10. The method of claim 1 wherein the level of expression of the RNA transcript is determined by a method comprising the steps of:

harvesting sample mRNA from the samples;

reverse transcribing the sample mRNA to form DNA;

ligating a promoter to the DNA;

transcribing in vitro using the DNA as a template to form test mRNA;

hybridizing the test RNA to an array of nucleic acid molecules.

11. The method of claim 1 wherein an immunoassay is performed to determine the level of expression.

12. A method of diagnosing cancer or determining p53 status in a sample suspected of being neoplastic, comprising the steps of:

comparing the level of expression of an RNA transcript or its translation product in a first sample of a first tissue to the level of expression of the transcript or translation product in a second sample of a second tissue, wherein the first tissue is suspected of being neoplastic and the second tissue is a normal human tissue, wherein the first and second tissue are of the same tissue type, and wherein the transcript is a transcript of a gene selected from the group consisting of 196105 PLACENTAL CALCIUM-BINDING PROTEIN (HUMAN), 127228 HEAT SHOCK PROTEIN, CHAPERONIN 10, or GroES;

MITOCHONDRIAL, H. sapiens Id1 mRNA, 51894 GTP-BINDING NUCLEAR PROTEIN RAN (Homo sapiens), 84680 ATP SYNTHASE ALPHA CHAIN, MITOCHONDRIAL PRECURSOR (HUMAN), Human non-histone chromosomal protein HMG-17 mRNA, complete cds, PHOSPHOGLYCERATE MUTASE, BRAIN FORM (HUMAN), Human mRNA (KIAAO108) or ORF (complete cds) and HepG2 mRNA identical sequence, 115413 HEAT SHOCK PROTEIN HSP 84 (Mus musculus), 78161 PROFILIN I (HUMAN), 124693 RAT mRNA for PROTEASOME SUBUNIT RC10-11, or HUMAN PROTEASOME SUBUNIT HSC10-11, 131036 TRANSFERRIN RECEPTOR PROTEIN (Homo sapiens), 214923 PSORIASIS-ASSOCIATED FATTY ACID BINDING PROTEIN HOMOLOG (HUMAN), Human mRNA (KIAA0098) for ORF (human counterpart of mouse chaperonin containing TCP-1 gene), partial cds, Human mRNA for ORF(KIAA0101), complete cds, 274422 ATPASE INHIBITOR, MITOCHONDRIAL (BOVIN), Human hnRNP A2 protein mRNA, 46019 MCM3 HOMOLOG (HUMAN), Human Ku autoimmune antigen gene, complete cds;

Homo sapiens pst1 mRNA for pancreatic secretory inhibitor (expressed in neoplastic tissue), Human esterase D mRNA 3′

end, 49970 LUPUS LA PROTEIN (HUMAN), H. sapiens mRNA for TRAP beta subunit, 125446 TRANSCRIPTION INITIATION FACTOR TFIID (Homo sapiens), Human mRNA for human homologue of rat phosphatidylethanolamine binding protein, complete cds, 120041 HLA-DR ASSOC. PROTEIN I, P31 (also called Ii, In, M1, Dr gamma, XM

     1) (Homo sapiens), Human protein-tyrosine phosphatase (HU-PP-1) mRNA, partial sequence, Homo spaiens integral nuclear envelope inner membrane protein (LBR) gene, complete cds, 52626 HYPOTHETICAL GTP-BINDING PROTEIN IN PMI40-PAC2 INTERGENIC REGION (Saccharomyces cervisiae), H. sapiens mRNA for ATP-citrate lyase, Human mRNA for ORF (KIAA0102), complete cds, 238612 Human bumetanide-sensitive NA-K-Cl cotransporter (NKCC1 or BSC2) mRNA, complete cds, 26573 STATHMIN (Homo sapiens), H. sapiens mRNA for DNA primase (subunit p48), Human c-myb mRNA, 3′

end, Human superoxide dismutase (SOD3 or EC-SOD) gene, complete cds, Huamn mRNA encoding IMP;

pyrophosphate phosphoribosyltransferase E.C. 2.4.2.8, Human synexin mRNA, complete cds, Human p62 mRNA, complete cds, Human mRNA for mitochondrial 3-oxoacyl-CoA thiolase, complete cds, Human mRNA (K1AA0094) for ORF (yeast methionine aminopeptidase-related), partial cds, 204299 REPLICATION PROTEIN A 14 KD SUBUNIT (HUMAN), H. sapiens mRNA for translin, 117708 MYOSIN HEAVY CHAIN, CLONE 203 (Hydra attenuata), Human mRNA (KIAA0088) for ORF (alpha-glucosidase-related), partial cds, Human mRNA (KIAA0035) for ORF (rat 140 kd nucleolar phosphoprotein homologue), partial cds, Human effector cell protease receptor-1 (EPR-1) gene, partial cds, 112020 C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC (HUMAN), 40874 TUBULIN GAMMA CHAIN (HUMAN), 42829 EUKARYOTIC INITATION FACTOR 4B (Hom sapiens), PROFILIN II (HUMAN), 40753 RAN-SPECIFIC GTPASE-ACTIVATING PROTEIN, ranGAP (Homo sapiens), Human mRNA for ORF (KIAK0002), or HUMAN D-TYPE CYCLIN complete cds, 128385 HAMSTER RNA FOR CYCLIN B2 (mesocricetus auratus), PYRROLINE-5-CARBOXYLATE REDUCTASE (HUMAN), 150169 EUKARYOTIC INITIATION FACTOR 4E (Homo sapiens), 72050 NUCLEOTIDE-SENSITIVE CHLORIDE CHANNEL (Canis familaris), or HUMAN CHLORIDE CHANNEL REGULATORY PROTEIN mRNA, Homo sapiens CD24 signal transducer mRNA, complete cds and 3′

region, H. sapiens mRNA for cathepsin C (dipeptidyl peptidase

     1), Homo sapiens monocarboxylate transporter 1 (SLC161A1) mRNA, complete cds, 68690 U1 SMALL NCULEAR RIBONUCLEOPROTEIN A (HUMAN), Human serine kinase (SRPK1) mRNA, complete cds, 209484 CD9 ANTIGEN (Bos taurus), or HUMAN T245 PROTEIN, Human glutamate dehydrogenase (GDH) mRNA, complete cds, 109334 NEGATIVE REGULATOR OF MITOSIS (Emericella nidulans), 77138 EUKARYOTIC INITIATION FACTOR 1A (Sac cerevisiae), or HUMAN PROTEIN SYNTHESIS FACTOR 4C(elF-4C), H. sapiens mRNA for neuromedin U, Human chonndroitin/dermatan sulfate proteoglycan (PG40) core protein mRNA, complete cds, H. sapiens mRNA for 2′

-5′

oligoadenylate binding protein, Human mRNA (KIAA0024) for ORF (putative human counterpart of chinese hamster phosphatidylserine synthase gene), complete cds, Human MAC30 mRNA, 3′

end, 74167 APOLIPOPROTEIN A-11 PRECURSOR (HUMAN), 36504 GTPASE ACTIVATING PROTEIN ROTUND (Drosophila melanogaster), 166353 CLEAVAGE STIMULATION FACTOR, 50 KD SUBUNIT (Homo sapiens), 127707 LAMININ BETA-1 CHAIN PRECURSOR (HUMAN), Human mRNA (K1AA0097) for ORF (novel protein), complete cds, 149556 O-antigen polymerase (Shigella flexneri), Homo sapiens E2F-related transcription factor (DP-1) mRNA, complete cds, NADH-UBIQUINONE DEHYDROGENASE 24 KD SUBUNIT PRECURSOR (HUMAN), Human methylmalonyl CoA mutase (MUT) gene, exon 13, 37866 BASIGIN PRECURSOR (Gallus gallus), 84443 GA BINDING PROTEIN BETA-1 CHAIN (Homo sapiens), Human erythroblastosis virus oncogene homolog 2 (ets-2) mRNA, complete cds, 53193 26S PROTEASE REGULATORY SUBUNIT 6 (Homo sapiens), S-ADENOSYLMETHIONINE DECARBOXYLASE PROENZYME (HUMAN), 26573 STATHMIN (Homo sapiens), 46827 VAV ONCOGENE (Hom sapiens), Human mRNA (KIAA0074) for ORF (yeast C728 protein-related), partial cds, Human DNA topoisomerase II gene (top2), gene 1, Homo sapiens cDNA clone 253186 3′

, 151010 EUKARYOTIC PEPTIDE CHAIN RELASE FACTOR SUBUNIT 1 (Homo sapiens), Human medium-chain acyl-CoA dehydrogenase (ACADM) mRNA, complete cds, and 121357 A49436 CDI1=CYCLIN-DEPENDENT KINASE INTERACTOR 1;

categorizing the first sample as neoplastic or as having a mutant p53 when expression is found to be higher in the first sample than in the second sample.

13. The method of claim 12 wherein a comparison of at least two of the transcripts or translation products is performed.

14. The method of claim 12 wherein a comparison of at least five of the transcripts or translation products is performed.

15. The method of claim 12 wherein a comparison of at least ten of the transcripts or translation products is performed.

16. The method of claim 12 wherein a comparison of at least twenty of the transcripts or translation products is performed.

17. The method of claim 12 wherein a comparison of at least 32 of the transcripts or translation products is performed.

18. The method of claim 12 wherein a comparison of at least fifty of the transcripts or translation products is performed.

19. The method of claim 12 wherein a comparison of 77 of the transcripts or translation products is performed.

20. The method of claim 12 wherein the level of expression of the RNA transcripts is determined using an array of nucleic acid molecules attached to a substrate in predetermined positions.

21. The method of claim 12 wherein the level of expression of the RNA transcript is determined by a method comprising the steps of:

harvesting sample mRNA from the samples;

reverse transcribing the sample mRNA to form DNA;

ligating a promoter to the DNA;

transcribing in vitro using the DNA as a template to form test mRNA;

hybridizing the test RNA to an array of nucleic acid molecules.

22. The method of claim 12 wherein an immunoassay is performed to determine the level of expression.

23. A method of diagnosing cancer or determining p53 status in a sample suspected of being neoplastic, comprising the steps of:

comparing the level of expression of at least one RNA transcript or its translation product selected from each of a first and a second group of RNA transcripts in a first sample of a first tissue to the level of expression of the at least one transcript or translation product in a second sample of a second tissue, wherein the first tissue is suspected of being neoplastic and the second tissue is a normal human tissue, wherein the first and second tissue are of the same tissue type, and wherein the first group of RNA transcripts consists of transcripts of genes selected from the group consisting of IG GAMMA-1 CHAIN C REGION (HUMAN), Human 1 g gamma3 heavy chain disease OMM protein mRNA, 274912 MYELIN TRANSCRIPTION FACTOR 1 (Homo sapiens), 152524 CYCLIN-DEPENDENT KINASE INHIBITOR 1 (Homo sapiens), H. sapiens mRNA for 43 kDa inositol polyphosphate 5-phosphatase, Human N-acetylgalactosamine 6-sulphatase (GALNS) gene, exon 14, 155730 KERATIN, TYPE I CYTOSKELETAL 17 (HUMAN), H. sapiens mRNA (clone

     9112), kinase related protein, Human placental cDNA coding for 5′

nucleotidase (EC 3.1.3.5), H. sapiens MLN62 mRNA, Human activated p21cdc42Ha kinase (ack) mRNA, complete cds., 81780 COMPLEMENT C4 PRECURSOR (Homo sapiens), 172486 clone, mRNA for tuberin, or TSC2 gene, Homo sapiens of cardiac alpha-myosin heavy chain gene, KERATIN, TYPE II CYTOSKELETAL 5 (HUMAN);

contains MSR1 repetive element, 182000 FK506-BINDING PROTEIN PRECURSOR (Mus musculus), Human insulin-like growth factor-binding protein-3 gene, complete Cds, clone HL1006d, 72466 ALPHA CRYSTALLIN B CHAIN (HUMAN), Homo sapiens mRNA for serum response factor-related protein, RSRFR2, 198656 HEPATOCYTE GROWTH FACTOR-LIKE PROTEIN PRECURSOR (Homo sapiens), 62461 SMALL NCUELAR RIBONUCLEORPORTEIN Particle N (SNRPN), contains MSR1 repetive element, 155335 INTEGRIN ALPHA-3 (Homo sapiens), 41792 TUBULIN BETA-2 CHAIN (HUMAN), Human estradiol 17 beta-dehydrogenase gene, complete cds, H. sapiens mRNA for cystathionine-beta-synthase, Homo sapiens of cardiac alpha-myosin heavy chain gene, Human mRNA for thyroglobulin, Human guanine nucleotide regulatory protein (ABR) mRNA, complete cds, Human novel growth factor receptor mRNA 3′

Cds, 142899 DNA-DIRECTED RNA POLYMERASE III LARGEST SUBUNIT (Plasmodium falciparum), Human mRNA for collagen VI alpha-1 C-terminal globular domain, Homo sapiens sodium channel type I, beta subunit (SCN1B) mRNA, complete cds., 50887 GUANINE NUCLEOTIDE DISSOCIATION STIMULATOR RALGDSA (Mus musculus), Human cytochrome P450 4F2 (CYP4F2) mRNA, complete cds, Human MAGE-2 gene exons 1-4, complete cds, H. sapiens mRNA for tansforming growth factor alpha, 38251 H sapiens HSJ1 mRNA, p53, H. sapiens mRNA for intestine-specific annexin, KERATIN, TYPE I CYTOSKELETAL 15 (HUMAN);

contains MER20 repetitive element, 5065 GROWTH ARREST AND DNA-DAMAGE-INDUCIBLE PROTEIN GADD45 (Homo sapiens), Human steroidogenic acute regulatory protein (StAR) mRNA, complete cds, LYSYL HYDROXYLASE (PLOD), (HUMAN), 151767 FASL RECEPTOR PRECURSOR (Homo sapiens), Homo sapiens creatine transporter mRNA, complete cds, KERATIN TYPE I CYTOSKELETAL 15 (HUMAN);

contains MER20 repetitive element, Human mRNA for thyroperoxidase, 275040 HEPATOCYTE GROWTH FACTOR-LIKE PROTEIN PRECURSOR (HUMAN);

121731 CYTOCHROME P450 IVB1 (Rattus norvegicus), Homo sapiens dopamine transporter (SLC6A3) mRNA, complete cds, 139080 COMPLEMENT DECAY-ACCELERATING FACTOR 1 PRECURSOR (Homo sapiens), H. sapiens mRNA for caveolin, Human endogenoous retrovirus type C onccovirus sequence, 31481 TYROSINE-PROTEIN KINASE HCK (Homo sapiens), Homo sapiens ribosomal protein S6 kinase 2 (RPS6KA2) mRNA, complete cds, Human Fas antigen (fas) mRNA, complete cds, Human mRNA encoding pregastrin (a regulatory hormone of gastric acid secretin and growth of the gastrointestinal mucosa), H. sapiens mRNA for placenta growth factor (PIGF), H. sapiens mRNA for placenta growth factor (PIGF), Human PML-2 mRNA, complet Cds, Human mRNA (KIAA0027) for ORF, partial cds, Human placenta-specific growth hormone mRNA, complete cds, Human high conductance inward rectifier potassium channel alpha subunit mRNA, complete cds, Human cytochrome P450 IID6 (CYP2D6) gene, complete cds, 180447 FIBROBLAST GROWTH FACTOR RECEPTOR 3 PRECURSOR (Homo sapiens), 153585 EBNA-2 NUCLEAR PROTEIN (Epstein-barr virus), 36678 TROPONIN C, ISOFORM 2 (Balanus nubilis), 182125 HDL-BINDING PROTEIN, HUMMLC2At;

Homo sapiens, 593 base pairs, 80486 LIVER CARBOXYLESTERASE PRECURSOR (HUMAN), 121916 NEUTRAL CALPONIN, SMOOTH MUSCLE (Sus scrofa), Human 11 beta-hydroxysteroid dehydrogenase type II mRNA, complete cds, Homo sapiens interferon regulatory factor 1 gene, complete cds, Human Fas antigen (fas) mRNA, complete cds, NEUTROPHIL OXIDASE FACTOR (p67 PHOX) (HUMAN), Human 11 kd protein mRNA, complete cds, Human semaphorin V mRNA, complete cds, MYELIN TRANSCRIPTION FACTOR 1 (HUMAN), 175991 NEURONAL CALCIUM SENSOR 1 (Rattus norvegicus), 81422 HUMAN SMOOTH MUSCLE ALPHA-ACTIN (AORTIC TYPE), Human mRNA for irp protein (int-1 related protein), Human Fas antigen (fas) mRNA, complete cds, Human beta-migrating plasminogen activator inhibitor 1 mRNA 3′

end, 26063 COMPLEMENT C4 PRECURSOR (Homo sapiens), 142450 VASCULAR ENDOTHELIAL GROWTH FACTOR PRECURSOR (Rattus norvegicus), Human visinin-like peptide 1 homolog mRNA, complete cds, H. sapiens mRNA for red cell anion exchanger (EPB3, Ae1, Band

     3) 3′

non-coding region, Human laminin S B3 chain (LAMB3) mRNA, complete cds, Human cytochrome P450 IID6 (CYP2D6) gene, complete cds, Human hexokinase 1 (HK1) mRNA, complete cds, Human mRNA for the MDM2 gene, Human mRNA for cytochrome P-450LTBV, RYANODINE RECEPTOR, SKELETAL MUSCLE (HUMAN), 39052 POTASSIUM CHANNEL PROTEIN EAG (Drosophila melanogaster), and 124416 SERINE THREONINE-PROTEIN KINASE COT-1 (Neurospora crassa), and wherein the second group of RNA transcripts consists of transcripts of genes selected from the group consisting of 196105 PLACENTAL CALCIUM-BINDING PROTEIN (HUMAN), 127228 HEAT SHOCK PROTEIN, CHAPERONIN 10, or GroES;

MITOCHONDRIAL, H. sapiens Id1 mRNA, 51894 GTP-BINDING NUCLEAR PROTEIN RAN (Homo sapiens), 84680 ATP SYNTHASE ALPHA CHAIN, MITOCHONDRIAL PRECURSOR (HUMAN), Human non-histone chromosomal protein HMG-17 mRNA, complete cds, PHOSPHOGLYCERATE MUTASE, BRAIN FORM (HUMAN), Human mRNA (KIAAO108) for ORF (complete cds) and HepG2 mRNA identical sequence, 115413 HEAT SHOCK PROTEIN HSP 84 (Mus musculus), 78161 PROFILIN I (HUMAN), 124693 RAT mRNA for PROTEASOME SUBUNIT RC10-11, or HUMAN PROTEASOME SUBUNIT HSC10-11, 131036 TRANSFERRIN RECEPTOR PROTEIN (Homo sapiens), 214923 PSORIASIS-ASSOCIATED FATTY ACID BINDING PROTEIN HOMOLOG (HUMAN), Human mRNA (KIAA0098) for ORF (human counterpart of mouse chaperonin containing TCP-1 gene), partial cds, Human mRNA for ORF(KIAA0101), complete cds, 274422 ATPASE INHIBITOR, MITOCHONDRIAL (BOVIN), Human hnRNP A2 protein mRNA, 46019 MCM3 HOMOLOG (HUMAN), Human Ku autoimmune antigen gene, complete cds, Homo sapiens pst1 mRNA for pancreatic secretory inhibitor (expressed in neoplastic tissue), HUMAN esterase D mRNA 3′

end, 49970 LUPUS LA PROTEIN (HUMAN), H. sapiens mRNA for TRAP beta subunit, 125446 TRANSCRIPTION INITIATION FACTOR TFIID (Homo sapiens), Human mRNA for human homologue of rat phosphatidylethanolamine binding protein, complete cds, 120041 HLA-DR ASSOC. PROTEIN I, P31 (also called Ii, In, M1, Dr gamma, XM

     1) (Homo sapiens), Human protein-tyrosine phosphatase (HU-PP-1) mRNA, partial sequence, Homo sapiens integral nuclear envelope inner membrane protein (LBR) gene, complete cds, 52626 HYPOTHETICAL GTP-BINDING PROTEIN IN PMI40-PAC2 INTERGENIC REGION (Saccharomyces cerevisiae), H. sapiens mRNA for ATP-citrate lyase, Human mRNA for ORF (KIAA0102), complete cds, 238612 Human bumetanide-sensitive NA-K-Cl cotransporter (NKCC1 or BSC2) mRNA, complete cds, 26573 STATHMIN (Homo sapiens), H. sapiens mRNA for DNA primase (subunit p48), Human c-myb mRNA, 3′

end, Human superoxide dismutase (SOD3 or EC-SOD) gene, complete cds, Human mRNA encoding IMP;

pyrophosphate phosphoribosyltransferase E.C. 2.4.2.8, Human synexin mRNA, complete cds, Human p62 mRNA, complete cds, Human mRNA for mitochondrial 3-oxoacyl-CoA thiolase, complete cds, Human mRNA (K1AA0094) for ORF (yeast methionine aminopeptidase-related), partial cds, 204299 REPLICATION PROTEIN A 14 KD SUBUNIT (HUMAN), H. sapiens mRNA for translin, 117708 MYOSIN HEAVY CHAIN, CLONE 203 (Hydra attenuata), Human mRNA (KIAA0088) for ORF (alpha-glucosidase-related), partial cds, Human mRNA (KIAA0035) for ORF (rat 140 kd nucleolar phosphoprotein homologue), partial cds, Human effector cell protease receptor-1 (EPR-1) gene, partial cds, 112020 C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC (HUMAN), 40874 TUBULIN GAMMA CHAIN (HUMAN), 42829 EUKARYOTIC INITATION FACTOR 4B (Hom sapiens), PROFILIN II (HUMAN), 40753 RAN-SPECIFIC GTPASE-ACTIVATING PROTEIN, ranGAP (Homo sapiens), Human mRNA for ORF (KIAK0002), or HUMAN D-TYPE CYCLIN complete cds, 128385 HAMSTER RNA FOR CYCLIN B2 (mesocricetus auratus), PYRROLINE-5-CARBOXYLATE REDUCTASE (HUMAN), 150169 EUKARYOTIC INITIATION FACTOR 4E (Homo sapiens), 72050 NUCLEOTIDE-SENSITIVE CHLORIDE CHANNEL (Canis familaris), or HUMAN CHLORIDE CHANNEL REGULATORY PROTEIN mRNA, Homo sapiens CD24 signal transducer mRNA, complete cds and 3′

region, H. sapiens mRNA for cathepsin C (dipeptidyl peptidase

     1), Homo sapiens monocarboxylate transporter 1 (SLC161A1) mRNA, complete cds, 68690 U1 SMALL NCULEAR RIBONUCLEOPROTEIN A (HUMAN), Human serine kinase (SRPK1) mRNA, complete cds, 209484 CD9 ANTIGEN (Bos taurus), or HUMAN T245 PROTEIN, Human glutamate dehydrogenase (GDH) mRNA, complete cds, 109334 NEGATIVE REGULATOR OF MITOSIS (Emericella nidulans), 77138 EUKARYOTIC INITIATION FACTOR 1A (Sac cerevisiae), or HUMAN PROTEIN SYNTHESIS FACTOR 4C(e1F-4C), H. sapiens mRNA for neuromedin U, Human chonndroitin/dermatan sulfate proteoglycan (PG40) core protein mRNA, complete cds, H. sapiens mRNA for 2′

-5′

oligoadenylate binding protein, Human mRNA (KIAA0024) for ORF (putative human counterpart of chinese hamster phosphatidylserine synthase gene), complete cds, Human MAC30 mRNA, 3′

end, 74167 APOLIPOPROTEIN A-11 PRECURSOR (HUMAN), 36504 GTPASE ACTIVATING PROTEIN ROTUND (Drosophila melanogaster), 166353 CLEAVAGE STIMULATION FACTOR, 50 KD SUBUNIT (Homo sapiens), 127707 LAMININ BETA-1 CHAIN PRECURSOR (HUMAN), Human mRNA (K1AA0097) for ORF (novel protein), complete cds, 149556 O-antigen polymerase (Shigella flexneri), Homo sapiens E2F-related transcription factor (DP-1) mRNA, complete cds, NADH-UBIQUINONE DEHYDROGENASE 24 KD SUBUNIT PRECURSOR (HUMAN), Human methylmalonyl CoA mutase (MUT) gene, exon 13, 37866 BASIGIN PRECURSOR (Gallus gallus), 8443 GA BINDING PROTEIN BETA-1 CHAIN (Homo sapiens), Human erythroblastosis virus oncogene homolog 2 (ets-2) mRNA, complete cds, 53193 26S PROTEASE REGULATORY SUBUNIT 6 (Homo sapiens), S-ADENOSYLMETHIONINE DECARBOXYLASE PROENZYME (HUMAN), 26573 STATHMIN (Homo sapiens), 46827 VAV ONCOGENE (Hom sapiens), Human mRNA (KIAA0074) for ORF (yeast C728 protein-related), partial cds, Human DNA topoisomerase II gene (top2), gene 1, Homo sapiens cDNA clone 253186 3′

, 151010 EUKARYOTIC PEPTIDE CHAIN RELASE FACTOR SUBUNIT 1 (Homo sapiens), Human medium-chain acyl-CoA dehydrogenase (ACADM) mRNA, complete cds, and 121357 A49436 CDI1=CYCLIN-DEPENDENT KINASE INTERACTOR 1;

categorizing the first sample as neoplastic or as having a mutant p53 when expression of at least one of the first group of RNA transcripts or translation products is found to be lower in the first sample than in the second sample, and expression of at least one of the second group of transcripts or translation products is found to be higher in the first sample than in the second sample.

24. The method of claim 23 wherein a comparison of at least two of the transcripts or translation products in each group of transcripts or translation products is performed.

25. The method of claim 23 wherein a comparison of at least five of the transcripts or translation products in each group of transcripts or translation products is performed.

26. The method of claim 23 wherein a comparison of at least ten of the transcripts or translation products in each group of transcripts or translation products is performed.

27. The method of claim 23 wherein a comparison of at least twenty of the transcripts or translation products in each group of transcripts or translation products is performed.

28. The method of claim 23 wherein a comparison of at least thirty of the transcripts or translation products in each group of transcripts or translation products is performed.

29. The method of claim 23 wherein a comparison of at least fifty of the transcripts or translation products in each group of transcripts or translation products is performed.

30. The method of claim 23 wherein a comparison of at least seventy of the transcripts or translation products in each group of transcripts or translation products is performed.

31. The method of claim 23 wherein the level of expression of the RNA transcripts is determined using arrays of nucleic acid molecules attached to a substrate in predetermined positions.

32. The method of claim 23 wherein the level of expression of the RNA transcript is determined by a method comprising the steps of:

harvesting sample mRNA from the samples;

reverse transcribing the sample mRNA to form DNA;

ligating a promoter to the DNA;

transcribing in vitro using the DNA as a template to form test mRNA;

hybridizing the test RNA to an array of nucleic acid molecules.

33. The method of claim 23 wherein an immunoassay is performed to determine the level of expression.