ctDNA Profiling to Identify DNA Damage Repair Gene Mutations in Prostate Cancer

A study observed concordance between gene alterations in DNA repair genes found in circulating tumor DNA (ctDNA) or metastatic tissue and primary prostate cancer.

“DNA damage repair (DDR) gene mutations represent actionable alterations that can guide precision medicine strategies for advanced prostate cancer. However, acquisition of contemporary tissue samples for molecular testing can be a barrier to deploying precision medicine approaches,” the researchers wrote. Their study was published in JAMA Oncology.

Data were collected from three cohorts: (1) FoundationOne, (2) University of Washington clinical cases (University of Washington–OncoPlex or Stand Up to Cancer–Prostate Cancer Foundation International Dream Team sequencing pipelines), and (3) University of Washington rapid autopsy series. Eligible patients had a DDR pathway mutation detected in metastatic tissue or ctDNA and available primary tissue sequencing for comparison. Clonal hematopoiesis of indeterminate potential (CHIP) and germline events were excluded, per the review of an expert molecular pathologist.

A total of 72 men were identified, and 21 who had ctDNA with only CHIP and/or germline events were excluded, leaving, leaving 51 for the final analysis. There was a median 55 months from acquisition of primary tissue to acquisition of ctDNA or tumor tissue. There was an 84% rate of concordance in DDR gene mutation status. When excluding patients with CHIP events, concordance rates remained similar. Two patients’ ctDNA presented multiclonal BRCA2 reversion mutations associated with resistance to PARP inhibitors and platinum chemotherapy.