AUTHOR=Chen Wei , Xia Wei , Xue Song , Huang Hang , Lin Qi , Liu Yi , Liu Tongtong , Zhang Yiqun , Zhang Panwang , Wang Jianfei , Yang Yining , Dong Baijun , Yu Zhixian 

TITLE=Analysis of BRCA Germline Mutations in Chinese Prostate Cancer Patients

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.746102

DOI=10.3389/fonc.2022.746102

ISSN=2234-943X

ABSTRACT=<p>Recent studies have indicated that prostate cancer (PCa) with <italic>BRCA2</italic> mutations is more aggressive. However, these reports mostly focused on Caucasus populations, and large-scale studies on <italic>BRCA</italic> mutations in Chinese PCa populations remain limited. Herein, we screened, from multiple centers in China, a total of 172 patients with PCa carrying <italic>BRCA1/2</italic> germline mutations. The variant distribution and type, associated somatic variant, and frequency of the <italic>BRCA</italic> germline variants in these patients were analyzed retrospectively. We found that Chinese patients with PCa carrying <italic>BRCA1/2</italic> germline mutations were diagnosed at an earlier age, i.e., 67 years (range, 34–89 years), and most had metastatic castration-resistant PCa (mCRPC) (54.65%, 94/172). The top three <italic>BRCA</italic> variants were frameshift, missense, and splicing variants. The overall pathogenic rates of the <italic>BRCA1</italic> and <italic>BRCA2</italic> variants were 17.46% (11/63) and 56.55% (82/145), respectively. Among the somatic mutations associated with <italic>BRCA2</italic> germline mutations, the highest frequency was for <italic>FOXA1</italic> (circulating tumor DNA [ctDNA] sequencing, 7.4%; tissue samples, 52%) and <italic>NCOR2</italic> mutations (ctDNA sequencing, 7.4%; tissue samples, 24%); <italic>TP53</italic> was the dominant somatic mutation associated with <italic>BRCA1</italic> germline mutations (ctDNA sequencing, 25%; tissue samples, 17%). Ultimately, in Chinese patients, PCa with <italic>BRCA1</italic>/2 germline mutations tends to be more aggressive. Compared with <italic>BRCA1</italic>, <italic>BRCA2</italic> has a higher frequency of germline pathogenic mutations. <italic>FOXA1</italic>, <italic>NCOR2</italic>, and <italic>TP53</italic> somatic mutations associated with higher <italic>BRCA1/2</italic> germline pathogenic mutations. Our description of <italic>BRCA</italic> germline mutations in the Chinese PCa patients provides more reference data for the precise diagnosis and treatment of Chinese PCa patients.</p>