Analysis of BRCA1/2 mutation spectrum and prevalence in unselected Chinese breast cancer patients by next-generation sequencing
Analysis of BRCA1/2 mutation spectrum and prevalence in unselected Chinese breast cancer patients by next-generation sequencing
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二代测序分析未选择的中国乳腺癌患者BRCA1/2突变谱和患病率
DOI：
10.1007/s00432-017-2465-8
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发表时间：
2017-10-01
影响因子：
3.6
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Li, Guoli;Guo, Xinwu;Wang, Jun
目的：BRCA 1和BRCA 2（BRCA 1/2）是两个主要的高转移率乳腺癌易感基因，其突变可导致乳腺癌的高风险和早发。为全面了解中国汉族乳腺癌患者BRCA 1/2基因突变的分布和发生率，并探讨BRCA 1/2基因突变与乳腺癌临床病理特征的关系，本研究采用微流控PCR靶点富集技术结合新一代测序技术，对313例中国汉族乳腺癌患者的配对肿瘤组织和正常组织进行BRCA 1/2基因突变检测。在313例患者中，分别有5例（1.60%）和12例（3.83%）检测到5个BRCA 1和8个BRCA 2有害生殖细胞突变。BRCA 1/2有害生殖系突变的总频率为5.43%。其中BRCA 1的c.1069A > T和c.3418_3419insTGACTACT、BRCA 2的c.8474_8487delCATACCCTATACAG和c.6547delG为新发现。此外，在313例患者中的31例（9.90%）中确定了32种意义不明的种系变异。我们还在10名患者中检测到13个体细胞突变（3.19%），其中4（1.28%）有害突变（BRCA 2中c.1575delT、c.2677C > T、c.7024C > T和c.7672G > T）和5个新突变（BRCA 1中c.4728A > G和c.4820T > C; BRCA 2中c.2527G > A、c.4069C > G和c.7672G > T）。BRCA 1/2基因突变携带者的年龄明显偏小，ER阴性和基底细胞样乳腺癌的发生率较高。结论：本研究为BRCA 1/2基因检测提供了一个可靠、有效的平台，并提示中国汉族乳腺癌患者中存在较高的BRCA 1/2基因突变率和特殊的突变谱。
Purpose:BRCA1 and BRCA2 (BRCA1/2) are two major high-penetrance breast cancer predisposition genes, mutations in which can lead to high risks and early onset of breast cancer. This study was performed to comprehensively investigate the spectrum and prevalence of BRCA1/2 mutations in unselected Chinese breast cancer patients and evaluate the associations of BRCA1/2 mutations with related clinicopathological characteristics of the tumors.Methods:By integrating microfluidic PCR-based target enrichment and next-generation sequencing, paired tumor and normal tissues from 313 unselected breast cancer patients were analyzed for both germline and somatic mutations of BRCA1/2 genes in Chinese Han population.Results:Total 5 BRCA1 and 8 BRCA2 deleterious germline mutations were detected in 5 (1.60%) and 12 (3.83%) of the 313 patients, respectively. The entire frequency of deleterious germline mutations of BRCA1/2 was 5.43%. Among them, c.1069A > T and c.3418_3419insTGACTACT in BRCA1, c.8474_8487delCATACCCTATACAG and c.6547delG in BRCA2 were novel. In addition, 32 germline variants of unknown significance in 31 (9.90%) of the 313 patients were identified. We also detected 13 somatic mutations in ten patients (3.19%), including 4 (1.28%) deleterious mutations (c.1575delT, c.2677C > T, c.7024C > T, and c.7672G > T in BRCA2) and 5 novel mutations (c.4728A > G and c.4820T > C in BRCA1; c.2527G > A, c.4069C > G and c.7672G > T in BRCA2). Notably, BRCA1 mutation carriers were significantly younger, and more likely to be ER negative and basal-like breast cancers.Conclusions:Our study provided a reliable and effective platform for BRCA1/2 genetic testing, and suggested that there was a relatively high prevalence and special spectrum of BRCA1/2 mutations in unselected Chinese breast cancer patients.