e13640 Background: Genetic testing for inherited mutations in DNA-repair genes such as BRCA1, BRCA2, ATM, PALP2, FANCA has been proposed for high-risk and metastatic prostate cancer patients for personalized therapy and management. Although the prevalence of germline DNA-repair gene mutations among Caucasian populations are known, the frequency of such mutations in Taiwan prostate cancer patients has not been established. In this study, we performed next-generation sequencing (NGS) analysis of BRCA1, BRCA2, ATM, PALP2, and FANCA in 49 prostate cancer patients stratified according to the NCCN risk criteria using blood sample collected from a single hospital center. Methods: 4ml whole blood samples are collected in EDTA tube from prostate cancer patients of low-intermediate, high to very high, regional, and metastatic risks. The samples are subjected to buffy coat fractionation, genomic DNA extraction, library preparation, full-exon NGS, and comparative analysis with all known germline variants. We identified and correlated the frequency of germline DNA-repair gene mutations with patient’s age at diagnosis, Gleason grades, initial PSA, family history of prostate cancer, and NCCN risk. Results: A total of 49 blood samples were tested and analyzed for BRCA1, BRCA2, ATM, PALP2, and FANCA mutations. Among all cases, 6.1% (3/49, 95% confidence interval [CI]: - 0.6%-12.8%) carried pathogenic mutations: 2.0% (1/49) in BRCA1, 2.0% (1/49) in BRCA2, and 2.0% (1/49) in ATM. They were compatible with previously reported mutations and no new germline variants were detected. These mutations were associated with initial PSA and NCCN risk; all identified mutations belonged to Gleason grade 5 and high to very high risk subgroups. No clinical association was observed with patient’s age of diagnosis and family history. Conclusions: In this single hospital center study, we observed a modest incidence of DNA-repair gene mutations in the Taiwan prostate cancer cohort. Germline DNA-repair gene mutations were observed in high risk prostate cancer patients with the highest Gleason grade. Frequencies of the mutations did not differ significantly according to age at diagnosis or family history of prostate cancer. These results were similar to the reported findings in the Caucasian populations. Our findings confirmed the necessity of genetic testing in Taiwan prostate cancer patients. [Table: see text]
Discussing the predictive, prognostic, and therapeutic value of germline DNA-repair gene mutations in metastatic prostate cancer patients
