World J Mens Health.  2026 Jan;44(1):194-202. 10.5534/wjmh.250093.

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

• Lee H
• Ho JN
• Song SH
• Oh JJ
• Huh JS
• Kim HM
• Kim KH
• Kim S
• Byun SS

• KMID: 2575468
• DOI: http://doi.org/10.5534/wjmh.250093

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.

Keyword

DNA; Mutation; Neoplasms; Prostate