Homologous recombination repair gene mutations in Chinese localized and locally advanced prostate cancer patients

Abstract

BackgroundHomologous recombination repair gene (HRR) mutations have been proven to be effective biomarkers for PARP inhibitor therapy for metastatic castration resistant prostate cancer. However, the frequency of HRR mutations in patients with localized and locally advanced prostate cancer is still unclear. This study investigated the profile of HRR gene mutations in Chinese localized and locally advanced prostate cancer patients. Materials and Methods74 patients with localized and locally advanced prostate cancer patients in Beijing Chaoyang Hospital between May 2018 and September 2019 were retrospectively included. Matched prostate cancer and histologically normal tissues were subjected to next-generation sequencing. Pathogenic alterations of 19 HRR genes were examined. ResultsTen deleterious and suspected deleterious mutations (4 germline and 6 somatic mutations) were detected in 9 of 74 (12.16 %) patients, occurred in seven HRR-related genes, including CDK12, NBN, ATM, ATR, BRCA2, PALB2 and RAD51C. The mutation frequency of HRR genes in this study (12.16 %) was higher than TCGA cohort (7.29 %), and the mutation sites in 7 HRR genes detected in this cohort were different from those of TCGA data. Patients with HRR gene mutations had higher Gleason grade (≥ 3) (P = 0.03) and risk level (very-high) (P = 0.03). Postoperative prostate specific antigen level and positive surgical margin rate was not associated with HRR gene mutation status. ConclusionsThis study illustrated the mutation patterns of HRR genes in Chinese population with localized and locally advanced prostate cancer. These results provide further evidence that HRR gene mutations were more prevalent in patients with higher Gleason grade, or with very-high-risk level. Patients with these clinicopathologic characteristics may need more precise stratification through molecular detection.