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.

1 . A method of analyzing circulating free DNA in a patient sample, comprising determining, in a sample that is blood, serum or plasma, the presence or absence or the amount of,
 a first cell-free DNA having a sequence falling within a first chromosomal region set forth in Table 2, Table 3, Table 4, or Table 5, and   a second cell-free DNA having a sequence falling within a second chromosomal region set forth in Table 2, Table 3, Table 4, or Table 5,   wherein the sequences of said first and second cell-free DNAs are free of repetitive elements.   
     
     
         2 . The method of  claim 1 , wherein said first and second chromosomal regions are different. 
     
     
         3 . The method of  claim 1 , wherein said patient is suspected of having prostate cancer. 
     
     
         4 . The method of  claim 1 , further comprising determining in said sample a third cell free DNA having a sequence falling within a third chromosomal region set forth in Table 2, Table 3, Table 4, or Table 5, 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. 
     
     
         5 . The method of  claim 1 , further comprising determining in said sample at least 5, 8, 10, 20, 30, or 40 additional different cell free DNAs each falling within a different chromosomal region set forth in Tables 2 and 3. 
     
     
         6 . The method of  claim 1 , wherein said chromosomal regions are all set forth within the same table. 
     
     
         7 . A kit comprising a plurality of oligonucleotides each having a nucleotide sequence falling within one same chromosomal region set forth in a table selected from the group consisting of Table 2, Table 3, Table 4, and Table 5, wherein said plurality includes a number of said oligonucleotides sufficient to detect all circulating cell-free DNA molecules derived from said chromosomal region. 
     
     
         8 . (canceled) 
     
     
         9 . The kit according to  claim 7 , wherein said oligonucleotides are attached to a solid substrate. 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . 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 first circulating cell-free DNA having a sequence falling within a first chromosomal region set forth in a table selected from the group consisting of Table 2, Table 3, and Table 4, and a second circulating cell-free DNA having a sequence falling within a second chromosomal region set forth in said table, wherein said first and second chromosomal regions are different, and wherein the sequences of said first and second cell free DNAs are free of repetitive element, and   correlating the presence of or an increased amount of said first and second cell free DNAs with an increased likelihood that said patient has prostate cancer.   
     
     
         13 .- 17 . (canceled) 
     
     
         18 . The method of  claim 12 , further comprising determining, in a sample that is blood, serum or plasma from said patient, the presence or absence or the amount of, a third circulating cell-free DNA having a sequence falling within a third chromosomal region set forth in said table, wherein the third chromosomal region is different from the first and second chromosomal region. 
     
     
         19 . The method of  12 , wherein the determining step comprises sequencing the CNA from the serum or plasma sample. 
     
     
         20 . The method of  claim 12 , wherein the determining step comprises contacting at least one probe that is selective for a chromosome region set forth in Table 2, Table 3, Table 4, or Table 5 with a DNA sample obtained from the serum or plasma sample from the patient under conditions in which the probe selectively hybridizes to a target sequence present on the chromosome region; and detecting hybridization of the probe. 
     
     
         21 . The method of  claim 20 , wherein the probe is attached to a solid surface. 
     
     
         22 . The method of  claim 20 , further comprising contacting the DNA sample with at least 20, 25, 30, 50, or 52 probes, wherein each probe is selective for a chromosome region set forth in Table 2, Table 3, Table 4, or Table 5. 
     
     
         23 . (canceled)