Prostate cancer associated circulating nucleic acid biomarkers

Abstract

The invention provides methods and reagents for diagnosing prostate cancer that are based on the detection of biomarkers in the circulating nucleic acids from a patient to be evaluated.

What is claimed is: 
     
         1 . A method of analyzing a sample from a patient for cell-free DNA associated with prostate cancer to calculate a numeric index of tumor-associated copy number variability , the method comprising:
 isolating cell-free DNA from a blood, serum, or plasma sample from the patient;   sequencing cell-free DNA molecules;   for each of a plurality of circulating cell-free DNA molecules, unambiguously assigning cell-free DNA sequences to a genomic region;   determining the normalized copy numbers of the plurality of cell-free DNA molecules;   comparing the normalized copy numbers to a reference value;   summing all regions that have a normalized copy number greater than that of 95% of the reference value; and   summing all regions that have a normalized copy number less than 5% of the reference value, to obtain a numeric index of tumor-associate copy number variability.   
     
     
         2 . The method of  claim 1 , wherein the reference value is derived from control subjects that are known to be cancer-free. 
     
     
         3 . The method of  claim 1 , wherein the reference value is derived from the patient, by comparing each region to all regions. 
     
     
         4 . The method of  claim 1 , wherein the index value is compared to the index value in cancer-free control subjects, where an index of >95% of that reference in indicative of cancer. 
     
     
         5 . A method of diagnosing or screening for prostate cancer in a patient, comprising:
 determining, in a sample that is blood, serum or plasma from said patient, the presence or absence or the amount of, a circulating cell-free DNA having a sequence falling within a chromosomal region set forth in a table selected from the group consisting of Table 2, Table 3, and Table 4; and   correlating the presence of or an increased amount of said circulating cell-free DNA with an increased likelihood that said patient has prostate cancer.