Biomarkers for prostate cancer metastasis

• US 20060110759A1
• Filed: 11/04/2005
• Published: 05/25/2006
• Est. Priority Date: 11/05/2004
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Collins, Colin C., Paris, Pamela L.
• Granted Patent: US 7,482,123 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6841 In situ hybridisation
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity

Abstract

The present invention provides genomic markers for determining the predisposition of prostate cancer to become metastasized.

Claims

1. A method of assessing the risk of post-prostatectomy reoccurrence of cancer in a individual, the method comprising,

detecting in a tumor sample from the individual the quantity of a MEN1 polynucleotide, wherein an individual with a risk of post-prostatectomy reoccurrence of cancer has an increased number of genomic copies of MEN1 per cell or increased expression of a MEN1 mRNA than a normal individual.

2. The method of claim 1, wherein the MEN1 polynucleotide is genomic DNA and an increased number of copies per cell of the genomic DNA is associated with a risk of post-prostatectomy reoccurrence of cancer.

3. The method of claim 1, wherein the MEN1 polynucleotide is a MEN1 mRNA or cDNA thereof and increased expression of the polynucleotide is associated with a risk of post-prostatectomy reoccurrence of cancer.

4. The method of claim 1, further comprising detecting the tumor sample a polynucleotide at at least one genomic location selected from the group consisting of 2qtel, 3q26.2, 3q26.32, 5p15.1, 7p22.3, 7q11.23, 7q11.22, 7q22.1, 7q31.31, 9q34.11, 11p15.5, 17q21.33, 17q25.3, 22q13.1, 4p13, 5q13.1, 5q14.3, 5q21.1, 5q21.2, 5q21.3, 5q23.1, 6q14.1, 6q21, 8p22, 8p21.2, 8p12, 10q23.31, 13q14.11, 13q14.13, 13q14.2, 13q14 and 16q23.1.

5. A method for determining the risk of metastasis of cancer in an individual who has or had prostate cancer, the method comprising,

detecting in a tumor sample from the individual the number of copies per cell of genomic DNA at at least one genomic location selected from the group consisting of 2qtel, 3q26.2, 3q26.32, 5p15.1, 7p22.3, 7q11.23, 7q11.22, 7q22.1, 7q31.31, 9q34.11, 11p15.5, 17q21.33, 17q25.3, 22q13.1, 4p13, 5q13.1, 5q14.3, 5q21.1, 5q21.2, 5q21.3, 5q23.1, 6q14.1, 6q21, 8p22, 8p21.2, 8p12, 10q23.31, 13q14.11, 13q14.13, 13q14.2, 13q14 and 16q23.1, wherein an increase in the number of copies per cell of DNA in genomic locations selected from the group consisting of 2qtel, 3q26.2, 3q26.32, 5p15.1, 7p22.3, 7q11.23, 7q11.22, 7q22.1, 7q31.31, 9q34.11, 11p15.5, 17q21.33, 17q25.3 and 22q13.1 and/or a decrease in the number of copies per cell of DNA in genomic locations selected from the group consisting of 4p13, 5q13.1, 5q14.3, 5q21.1, 5q21.2, 5q21.3, 5q23.1, 6q14.1, 6q21, 8p22, 8p21.2, 8p12, 10q23.31, 13q14.11, 13q14.13, 13q14.2, 13q14 and 16q23.1, compared to the number of copies per cell in non-cancer cells, indicates an increased risk of metastasis.

6. The method of claim 5, comprising detecting the number of copies per cell at least two of the genomic locations.

7. The method of claim 5, comprising detecting the number of copies per cell at least six of the genomic locations.

8. The method of claim 5, comprising detecting the number of copies per cell at 2qtel, 3q26.2, 3q26.32, 5p15.1, 7p22.3, 7q11.23, 7q11.22, 7q22.1, 7q31.31, 9q34.11, 11p15.5, 17q21.33, 17q25.3, 22q13.1, 4p13, 5q13.1, 5q14.3, 5q21.1, 5q21.2, 5q21.3, 5q23.1, 6q14.1, 6q21, 8p22, 8p21.2, 8p12, 10q23.31, 13q14.11, 13q14.13, 13q14.2, 13q14 and 16q23.1.

9. The method of claim 5, comprising detecting the number of copies of genomic DNA that hybridizes to at least one BAC selected from the group consisting of CTB-172I13, RP11-1146E5, RP11-114M1, RP1-97B16, RP11-88L18, RP11-23D23, CTC-329F6, RP1-117G9, RP11-96016, RP11-213E22, CTD-2041G23, RP11-1704, RP4-693L23, RP5-1071I14, RP11-46E14, RMC22P003, RP11-253O5, RP11-267K19, RP11-135F5, RP11-203J7, RP11-115L24, CTD-2079J2, RP11-73N22, RP11-217L13, RP11-28L24, RP11-47E20, RP11-182G2, RP11-76B12, RP11-232J22, CTD-2015D3, RP11-5713, RP11-129G17, RP11-14A4, CTD-2202J2, RP11-17I11, RP11-217H23, CTD-2173J2, RP1-269F22, and RP11-12H11.

10. The method of claim 5, comprising detecting the number of copies of genomic DNA in a gene selected from the group consisting of EV11, PIK3CA, EIF3S9, ELN, AUTS2, VGF, Serpine1, PLOD3, AP1S1, CORTBP2, p57 (KIP2), NGFR, CBX4, CBX8, PDGFB, FER, TUBE1, LAMA4, BVES, POPDC3, TUSC3, DOCK5, BNIP3L, ADRA1, NRG1, LHFP, GTF2F2, RB1 and CHC1L.

11. A method of determining the stage of a prostate cancer tumor, the method comprising,

detecting in a tumor sample from the individual the quantity of a CSMD1 polynucleotide, wherein an individual with an advanced stage of prostate cancer has fewer genomic copies of CSMD1 per cell or reduced expression of a CSMD1 mRNA than a normal individual.

12. The method of claim 11, wherein the CSMD1 polynucleotide is genomic DNA and a decreased number of copies per cell of the genomic DNA is associated with an advanced stage of prostate cancer.

13. The method of claim 11, wherein the CSMD1 polynucleotide is a CSMD1 mRNA or cDNA thereof and decreased expression of the polynucleotide is associated with an advanced stage of prostate cancer.

14. The method of claim 11, further comprising detecting the tumor sample a polynucleotide at at least one genomic location selected from the group consisting of 2qtel, 3q26.2, 3q26.32, 5p15.1, 7p22.3, 7q11.23, 7q11.22, 7q22.1, 7q31.31, 9q34.11, 11p15.5, 17q21.33, 17q25.3, 22q13.1, 4p13, 5q13.1, 5q14.3, 5q21.1, 5q21.2, 5q21.3, 5q23.1, 6q14.1, 6q21, 8p22, 8p21.2, 8p12, 10q23.31, 13q14.11, 13q14.13, 13q14.2, 13q14 and 16q23.1.

15. A method of identifying an agent that inhibits prostate cancer proliferation or metastasis, the method comprising,

contacting a plurality of agents to a cell expressing a polypeptide selected from the group consisting of the gene products listed in Table 2;

selecting an agent that modulates expression or activity of the polypeptide; and

determining whether the selected agent inhibits prostate cancer proliferation or metastasis, thereby identifying an agent that inhibits prostate cancer proliferation or metastasis.

16. An agent selected according to claim 15.

17. A method of treating prostate cancer or inhibiting metastasis of prostate cancer, the method comprising,

administrating to an individual in need thereof an agent selected according to claim 15.