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Germline Variants Provide Insight Into Tumor Growth in Prostate Cancer

Caroline Seymour
Published: Wednesday, Dec 04, 2019

Paul C. Boutros, PhD

Paul C. Boutros, PhD

Select DNA variants leading to methylation dysregulation within the germline DNA of men with localized prostate cancer were found to be predictive of disease biology, suggesting the prognostic capacity of inherited elements of a patient’s genome, according to data published in Nature Medicine.1,2

Significant tumor-specific variants associated with microRNA expression are summarized according to the single nucleotide polymorphism, methylation probe, and gene identified, respectively:
  • rs1225741, cg13351621, SYCP2L
  • rs16934152, cg13558087, POLR1E
  • rs2456274, cg08881796, VPS53
  • rs2570972, cg08367326, AMIGO1
  • rs3761188, cg09328228, PABPC1L
  • rs3761188, cg15588266, PABPC1L
  • rs3764509, cg14963724, CNDP2
  • rs3807032, cg24330456, RNF39
  • rs3807033, cg05563515, RNF39
  • rs3807033, cg17322683, RNF39
  • rs3807033, cg23793213, RNF39
  • rs3849767, cg18264728, DAB2
  • rs4147470, cg03997398, ABLIM3
  • rs4147470, cg04669407, ABLIM3
  • rs9261309, cg13918754, RNF39
  • rs9261309, cg20249327, RNF39
  • rs9295763, cg20249327, ELOVL2
Investigators selected 58 methylation probes based on their association with biochemical recurrence, defined by increasing prostate-specific antigen levels after primary therapy. Notably, not all methylation probes triggered tumor-specific changes in DNA methylation. Only 28% of the methylation probes that were associated with a higher likelihood of biochemical recurrence were targeted by changes in DNA methylation.
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