Characteristics of Germline and Somatic Mutations of DNA Repair Genes in Korean Men with Prostate Cancer

Abstract

Purpose: While the association between defect of DNA damage repair (DDR) genes and prostate cancer (PCa) risk is wellestablished, there has been a lack of data in East Asian population. This study reports contemporary prevalence of DDR genes mutations in Korean PCa patients. Materials and Methods: We analysed samples from 1, 316 patients with PCa in Korea. Whole genome sequencing and targeted cancer panel sequencing were employed for genetic analysis. A total of 26 DDR genes were analysed based on the previous literature. Results: Germline mutation profiling was conducted in 1, 026 patients, identifying 66 mutations (6.4%) at 14 genes. Somatic mutation profiling in 550 patients revealed 105 mutations (19.1%) at 15 genes. While BRCA2 was most frequent (3.4%) among germline mutations, CDK12 was most frequent (6.5%) among somatic mutations in our study. Patients with metastatic disease showed significantly higher mutation frequency than patient with localized disease in both germline and somatic mutation (both p-value<0.05). There were statistically positive correlation between increase of grade group and higher frequency in both germline and somatic DDR gene mutations (p<0.001). The patients with higher stage showed significantly higher rate of DDR gene mutation in germline analysis (p<0.001) but not in somatic analysis (p=0.888). Conclusions: BRCA2 was the most prevalent in germline mutations but CDK12 was out-numbered BRCA2 in somatic mutations in the present study. The higher frequency of DDR gene mutation was associated with advanced cancer stage and higher cellular grade group. © 2026 Korean Society for Sexual Medicine and Andrology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.