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. 2022 Feb 17:12:746102.
doi: 10.3389/fonc.2022.746102. eCollection 2022.

Analysis of BRCA Germline Mutations in Chinese Prostate Cancer Patients

Wei Chen  1 , Wei Xia  2 , Song Xue  3 , Hang Huang  1 , Qi Lin  1 , Yi Liu  4 , Tongtong Liu  5 , Yiqun Zhang  5 , Panwang Zhang  5 , Jianfei Wang  5 , Yining Yang  5 , Baijun Dong  6 , Zhixian Yu  1
Affiliations

Analysis of BRCA Germline Mutations in Chinese Prostate Cancer Patients

Wei Chen et al. Front Oncol. .

Abstract

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

Keywords: BRCA variants; BRCA1 and BRCA2 germline mutations; pathogenic rate; prostate cancer in China; somatic mutation.

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Conflict of interest statement

Authors TL, YZ, PZ, JW and YY were employed by company GloriousMed Clinical Laboratory Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Frequency distribution of pathogenic and non-pathogenic BRCA1 and BRCA2 mutations in patients with PCa. VUS, variants of uncertain significance.
Figure 2
Figure 2
The distribution of various BRCA1/2 variant types on full‐length BRCA1/2 exons. (A, B), The distribution of four variant types on BRCA1 (A) and BRCA2 (B). The scheme of exons (blue bar at the bottom of each panel) is shown as the reference. (C) The number of different variants (inner ring) and number of variant carriers (outer ring). Colors represent different variant types.
Figure 3
Figure 3
Interpretation of pathogenicity and distribution of pathogenic and non-pathogenic variants in full-length BRCA1/2 genes. (A, B) The number of variants in each exon of the BRCA1 (A) and BRCA2 (B) gene. (C, D), The number of variants normalized to exon length for BRCA1 (C) and BRCA2 (D). (E, F) The relative ratio of each type of pathogenicity in each type of variant in BRCA1 (E) and BRCA2 (F).
Figure 4
Figure 4
Genomic landscape of patients with PCa with BRCA germline pathogenic mutations. (A) Blood samples. (B) Tissue samples. TSS, translation start site.
See this image and copyright information in PMC

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