Methods for Diagnosing Prostate Cancer and Predicting Prostate Cancer Relapse

Abstract

The present invention relates to methods and compositions for diagnosing prostate cancer and/or determining whether a prostate cancer patient is at increased risk of suffering a relapse, or a rapid relapse, of his cancer. It is based, at least in part, on the results of a comprehensive genome analysis on 241 prostate cancer samples (104 prostate cancer, 85 matched bloods, 49 matched benign prostate tissues adjacent to cancer, and 3 cell lines) which indicate that (i) genome copy number variation (CNV) occurred in both cancer and non-cancer tissues, and (ii) CNV predicts prostate cancer progression.

What is claimed is: 
     
         1 . A method of diagnosing a prostate cancer in a subject comprising determining the number and/or size of copy number variations in DNA from a tumor sample, a sample of tissue adjacent a tumor, and/or in a blood sample, where if the number and/or size of copy number variations exceeds a particular threshold, a diagnosis of prostate cancer is indicated. 
     
     
         2 . The method of  claim 1 , comprising determining the number and size of copy number variations in DNA from a tumor or prostate tissue sample, where if the number of copy number variations exceeds 90 loci, each locus being at least 10 kb in length, a diagnosis of prostate cancer is indicated 
     
     
         3 . The method of  claim 1 , where said subject is a male having one or more of the following clinical findings: increased serum prostate specific antigen, enlarged prostate on physical exam, difficulty urinating and/or urinary retention, comprising determining the number and/or size of copy number variations in DNA from a blood sample from the subject, where if the number of copy number variations exceeds 4 loci, each locus being at least 10 kb in length, a diagnosis of prostate cancer is indicated. 
     
     
         4 . The method of  claim 1 , comprising determining the presence of deletions in one or more of chromosome regions 8p, 13p, 16q, and/or 17p in DNA from a prostate tissue or a blood sample from the subject, where if there is a deletion of at least 3 megabases in one or more of these regions, a diagnosis of prostate cancer is indicated. 
     
     
         5 . The method of  claim 1 , comprising determining the presence of amplification in one or more of chromosome regions 8q and X in DNA from a prostate tissue or a blood sample from the subject, where if there is amplification of a locus in one or more of these regions, a diagnosis of prostate cancer is indicated. 
     
     
         6 . A method of determining that a prostate cancer patient is at decreased risk for relapse or rapid relapse comprising determining the size of copy number variations in a prostate tumor sample, tissue adjacent a prostate tumor, and/or blood, where if the size of copy number variations is below a particular threshold, the patient is deemed to be at decreased risk for relapse or rapid relapse. 
     
     
         7 . The method of  claim 6 , comprising determining the mean size of copy number variations in DNA from a blood sample from the patient, where if the mean size of copy number variations is 40 kb or less, the patient is deemed to be at decreased risk for relapse. 
     
     
         8 . The method of  claim 6 , comprising determining the mean size of copy number variations in DNA from a sample of tissue adjacent a prostate cancer from the patient, where if the mean size of copy number variations is 95 kb or less, the patient is deemed to be at decreased risk for relapse. 
     
     
         9 . The method of  claim 6 , comprising determining the mean size of copy number variations in DNA from a sample of prostate cancer tissue from the patient, where if the mean size of copy number variations is 385 kb or less, the patient is deemed to be at decreased risk for relapse. 
     
     
         10 . The method of  claim 6 , comprising determining the median size of copy number variations in a blood sample from the patient, where if the median size of copy number variations is 17 kb or less, the subject is deemed to be at decreased risk for relapse. 
     
     
         11 . The method of  claim 6 , comprising determining the median size of copy number variations in a sample of tissue adjacent a prostate cancer from the patient, where if the median size of copy number variations is 16 kb or less, the subject is deemed to be at decreased risk for relapse. 
     
     
         12 . The method of  claim 6 , comprising determining the median size of copy number variations in DNA from a sample of prostate cancer tissue from the patient, where if the median size of copy number variations is 185 kb or less, the patient is deemed to be at decreased risk for relapse. 
     
     
         13 . A method of determining that a prostate cancer patient is at increased risk for relapse or rapid relapse comprising determining the size of copy number variations in a prostate tumor sample, tissue adjacent a prostate tumor, and/or blood, where if the size of copy number variations exceeds a particular threshold, the patient is deemed to be at increased risk for relapse or rapid relapse. 
     
     
         14 . The method of  claim 12 , comprising determining the mean size of Copy number variations in a prostate tumor sample, tissue adjacent a prostate tumor, and/or blood, where if the mean size of copy number variations exceeds a particular threshold, the patient is deemed to be at increased risk for relapse or rapid relapse. 
     
     
         15 . The method of  claim 13 , comprising determining the mean size of copy number variations in DNA from a blood sample from the patient, where if the mean size of copy number variations is 70 kb or more, the patient is deemed to be at increased risk for relapse. 
     
     
         16 . The method of  claim 14 , comprising determining the mean size of copy number variations in DNA from a sample of tissue adjacent to prostate cancer from the patient, where if the mean size of copy number variations is 246 kb or more, the patient is deemed to be at increased risk for relapse. 
     
     
         17 . The method of  claim 14 , comprising determining the mean size of copy number variations in DNA from a sample of prostate cancer tissue from the patient, where if the mean size of copy number variations is 817 kb or more, the patient is deemed to be at increased risk for relapse. 
     
     
         18 . The method of  claim 14 , comprising determining the mean size of copy number variations in DNA from a sample of prostate cancer tissue from the patient, where if the mean size of copy number variations is 1060 kb or more, the patient is deemed to be at increased risk for rapid relapse. 
     
     
         19 . The method of  claim 13 , comprising determining the median size of copy number variations in a prostate tumor sample, tissue adjacent a prostate tumor, and/or blood, where if the median size of copy number variations exceeds a particular threshold, the patient is deemed to be at increased risk for relapse or rapid relapse. 
     
     
         20 . The method of  claim 19 , comprising determining the median size of copy number variations in DNA from a blood sample from the patient, where if the median size of copy number variations is 23 kb or more, the patient is deemed to be at increased risk for relapse. 
     
     
         21 . The method of  claim 19 , comprising determining the median size of copy number variations in DNA from a sample of tissue adjacent a prostate cancer from the patient, where if the median size of copy number variations is 18 kb or more, the patient is deemed to be at increased risk for relapse. 
     
     
         22 . The method of  claim 19 , comprising determining the median size of copy number variations in DNA from a sample of prostate cancer tissue from the patient, where if the median size of copy number variations is 647 kb or more, the patient is deemed to be at increased risk for relapse.