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Yi Liang, Xuexi Yang, Hong Li, Anna Zhu, Zhiwei Guo, Ming Li
(School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China (mainland))
Med Sci Monit 2018; 24:2465-2475
BRCA1 and BRCA2 (BRCA1/2) play important roles in the development of breast cancer, but information regarding BRCA1/2 mutations in Chinese females remains limited. The aim of this study was to investigate the prevalence and spectrum of BRCA1/2 mutations in China.
MATERIAL AND METHODS: In total, 595 breast cancer patients in China were screened with an amplicon-based panel for the detection of BRCA1/2 mutations in coding regions using next-generation sequencing (NGS) with a Personal Genome Machine. Every pathogenic mutation detected was confirmed by Sanger sequencing. The disease-causing potential of variants of uncertain significance (VUS) was predicted using PolyPhen-2, SIFT, PhyloP, and Grantham.
RESULTS: The prevalence of BRCA1/2 mutations was 8.07% in the Chinese population. Forty-two pathogenic mutations were identified in 48 cases (17 BRCA1 cases and 31 BRCA2 cases), including 19 novel mutations. Nine VUS were predicted to be deleterious by PolyPhen-2 and SIFT and subsequently predicted by PhyloP and Grantham for the evolutionary conservation.
CONCLUSIONS: These results suggest that NGS is useful as a rapid, high-throughput, and cost-effective screening tool for the analysis of BRCA1/2 mutations. Based on this panel, we found that BRCA1/2 germline mutations in China exhibit distinct characteristics compared to those in Western populations.