Prostate cancer associated circulating nucleic acid biomarkers
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 cell-free DNA in a sample from a patient that has or is suspected of having prostate cancer, 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 nucleotides in length unambiguously assigned to a first chromosomal region set forth in Table 4, and
a second cell-free DNA having a sequence at least 25 nucleotides in length unambiguously assigned to a second chromosomal region set forth in Table 4 that is different from the first,
wherein the sequences of said first and second cell-free DNAs are free of repetitive elements.
2. The method of claim 1 , further comprising determining 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 4, 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.
3. The method of claim 1 , further comprising measuring in said sample the level of at least 5, 8, 10, 15, or 20 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 4.
4. The method of claim 1 further comprising effecting a prostate cancer therapy.
5. The method of claim 1 , further comprising measuring the level of all cell-free DNAs in the sample that have a sequence at least 25 nucleotides in length free of repetitive elements unambiguously assigned to a chromosomal region listed in Table 4.
6. A method of treating a patient for prostate cancer, the method comprising:
determining whether a human patient that has or is suspected of having prostate cancer, has a change in copy number of a chromosomal region set forth in Table 4 by:
obtaining or having obtained a nucleic acid sample from blood, serum, or plasma from the patient and
performing or having performed sequencing of nucleic acids obtained from the nucleic acid sample to determine copy number changes of chromosomal regions set forth in Table 4 by determining the level of a nucleic acid sequence of at least 25 nucleotides in length that is free of repetitive elements and unambiguously assigned to each of the chromosomal regions set forth in Table 4 and
effecting a therapy for prostate cancer if the patient has: an increase in copy number of a sequence of at least 25 nucleotides in length unambiguously assigned to chromosome 8 region 43050001-43250000, chromosome 17 region 58300001-58500000, chromosome 15 region 61500001-61900000, chromosome 1 region 148450001-148650000, chromosome 10 region 17900001-18200000; chromosome 9 region 88650001-88750000, chromosome 10 89050001-89250000, chromosome 10 region 27650001-27850000, chromosome 6 region 58450001-58550000, chromosome 20 region 57850001-58250000, chromosome 20 region 42300001-42700000, chromosome 8 region 120750001-120950000, chromosome 12 region 44300001-44400000, chromosome 12 region 109500001-109600000, chromosome 7 region 86350001-86450000, chromosome 2 region 186650001-186750000, chromosome 2 region 98700001-98900000, or chromosome 12 region 95400001-95600000; or
has a decrease in copy number of a sequence of at least 25 nucleotides in length unambiguously assigned to chromosome 1 region 212200001-212400000, chromosome 13 region 21250001-21750000, chromosome 13 region 21300001-21800000, chromosome 4 region 186600001-187100000, chromosome 13 region 18350001-18650000, chromosome 2 region 47750001-47850000, or chromosome 17 region 61300001-61800000.