AMACR cancer markers

• US 20050136493A1
• Filed: 07/30/2004
• Published: 06/23/2005
• Est. Priority Date: 08/02/2001
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Rubin, Mark A., Chinnaiyan, Arul M., Sreekumar, Arun, Laxman, Bharathi
• Granted Patent: US 7,332,290 B2
• Time in Patent Office: Days
• US Class Current: 435/7.230
• CPC Class Codes: C07K 16/3069 Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C12Q 1/533 involving isomerase
• 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: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2474/20 Immunohistochemistry assay
• CPC Class Codes: G01N 33/57434 of prostate
• CPC Class Codes: Y10S 436/813 Cancer

Abstract

The present invention relates to compositions and methods for cancer diagnostics, including but not limited to, cancer markers. In particular, the present invention provides gene expression profiles associated with prostate cancers. The present invention also provides novel markers useful for the diagnosis, characterization, and treatment of prostate cancers. In particular, the present invention provides methods and compositions for the use of α-methylacyl-CoA racemase (AMACR) as a marker for prostate cancer detection and prognosis.

Claims

1. A method of detecting the presence or absence of α

-methylacyl-CoA racemase in urine, comprising;

a) providing

i) urine from a subject;

ii) a reagent for detecting α

-methylacyl-CoA racemase in said urine; and

b) contacting said urine with said reagent under conditions such that said reagent detects the presence or absence of α

-methylacyl-CoA racemase in said urine.

2. The method of claim 1, wherein the level of said α

-methylacyl-CoA racemase in said urine is determined.

3. The method of claim 2, wherein said minimum threshold level is set to 1, where 0 is absence of α

-methylacyl-CoA racemase and 4 is highest level expression.

4. The method of claim 3, wherein the presence of said α

-methylacyl-CoA racemase in said urine at a level above said minimum threshold level is indicative of a diagnosis of cancer in said subject.

5. The method of claim 4, wherein said cancer is prostate cancer.

6. The method of claim 1, wherein said reagent is an antibody.

7. The method of claim 6, wherein said antibody is selected from the group consisting of a single chain antibody, an Fab, and an epitope-binding fragment of an antibody.

8. The method of claim 1, wherein said reagent comprises a label.

9. The method of claim 8, wherein said label is selected from the group consisting of a radioactive label, a fluorescent label, a chemiluminescent label, and a bioluminescent label.

10. A kit for detecting the presence or absence of prostate cancer in a subject, comprising:

a) a reagent capable of specifically detecting the presence or absence of α

-methylacyl-CoA racemase in urine; and

b) instructions for using said kit for detecting said α

-methylacyl-CoA racemase in said urine.

11. The kit of claim 10, wherein said reagent comprises an antibody that specifically binds to an α

-methylacyl-CoA racemase polypeptide.

12. The kit of claim 11, wherein said reagent comprises a label.

13. The kit of claim 12, wherein said label is selected from the group consisting of a radioactive label, a fluorescent label, a chemiluminescent label, and a bioluminescent label.

14. The kit of claim 10, wherein said instructions comprise instructions for determining whether said levels of said α

-methylacyl-CoA racemase in said urine are above a minimum threshold value.

15. A method for determining risk of prostate cancer progression in a subject, comprising:

a) providing a prostate cancer tissue sample from said subject;

b) detecting the presence or absence of α

-methylacyl-CoA racemase in said sample; and

c) determining that said subject is at increased risk for prostate cancer progression if said α

-methylacyl-CoA racemase levels are below a maximum threshold value.

16. The method of claim 15, wherein said prostate cancer tissue sample is obtained by surgical resection from said subject.

17. The method of claim 15, wherein said prostate cancer progression comprises prostate specific antigen failure.

18. The method of claim 15, wherein said prostate cancer progression comprises prostate cancer-specific death.

19. The method of claim 15, wherein said detecting the presence of α

-methylacyl-CoA racemase comprises detecting an α

-methylacyl-CoA racemase polypeptide.

20. The method of claim 19, wherein said detecting the presence of an α

-methylacyl-CoA polypeptide comprises exposing said prostate cancer tissue sample to an antibody specific to said α

-methylacyl-CoA racemase polypeptide and detecting the binding of said antibody to said polypeptide.

21. The method of claim 20, wherein said antibody is detectably labeled.

22. The method of claim 21, wherein said detectable label is selected from the group consisting of a radioactive label, a fluorescent label, a chemiluminescent label, and a bioluminescent label.

23. The method of claim 19, wherein said α

-methylacyl-CoA racemase polypeptide is detected and quantified by a semi-automated image analysis system.

24. The method of claim 15, wherein said subject comprises a human subject.