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 circulating free DNA in a patient sample, comprising measuring, in a sample that is blood, serum or plasma, the level of,
 a first cell-free DNA having a sequence at least 25 nucleotide in length unambiguously assigned to a first chromosomal region set forth in Table 1, and   a second cell-free DNA having a sequence at least 25 nucleotide in length unambiguously assigned to a second chromosomal region set forth in Table 1,   wherein the sequences of said first and second cell-free DNAs are free of repetitive elements.   
     
     
         2 . The method of  claim 1 , wherein said patient has or is suspected of having prostate cancer. 
     
     
         3 . The method of  claim 1 , further comprising measuring in said sample the level of a third cell free DNA having a sequence at least 25 nucleotides in length unambiguously assigned to a third chromosomal region set forth in Table 1, wherein said third chromosomal region is different from said first and second chromosomal regions, and the sequence of said third cell free DNA is free of repetitive elements. 
     
     
         4 . The method of  claim 1 , further comprising measuring in said sample at least 5, 8, 10, 20, 30, 40, 50, 60, 70, 75, 80, 85, or 90 additional different cell free DNAs, each having a sequence at least 25 nucleotides in length and free of repetitive elements, wherein each sequence is unambiguously assigned to a different chromosomal region set forth in Table 1. 
     
     
         5 . The method of  claim 1 , further comprising measuring the level of all of the cell-free DNAs in the sample that have a sequence at least 25 nucleotides in length unambiguously assigned to a chromosomal region listed in Table 1. 
     
     
         6 . The method of  claim 1 , further comprising effecting a cancer therapy. 
     
     
         7 . A kit comprising:
 a first plurality of oligonucleotides wherein each oligonucleotide within each of said plurality has a nucleotide sequence falling within the same first chromosomal region set forth in Table 1; and   a second plurality of oligonucleotides each having a nucleotide sequence falling within the same second chromosomal region set forth in Table 1, wherein said first and second chromosomal regions are different and wherein said oligonucleotides are free of repetitive element.   
     
     
         8 . The kit according to  claim 7 , wherein the first chromosomal region and the second chromosomal region are set forth in Table 4. 
     
     
         9 . The kit according to  claim 7 , wherein said oligonucleotides are attached to a solid substrate. 
     
     
         10 . A method of analyzing DNA in a patient sample, comprising:
 preparing a sequencing library of circulating cell-free DNA by performing whole genome amplification on cell-free DNA isolated from the blood, serum or a plasma sample from a patient;   sequencing DNA from the sequencing library;   unambiguously assigning the sequences to a region of the human genome to identify genomic windows that represent the regions of the genome that comprise the sequences;   determining genomic windows for which the number of reads significantly differ from normal controls.   
     
     
         11 . The method of  claim 11 , wherein the number of windows that deviate from normal is determined and compared to normal controls. 
     
     
         12 . The method of  claim 11 , wherein the sum of reads in one or more windows is determined and compared to normal. 
     
     
         13 . The method of  claim 11 , wherein the patient has prostate cancer.