中国中部地区乳腺癌遗传易感基因BRCA1/2高通量测序情况分析

Analysis of breast cancer susceptibility gene BRCA1/2 by next-generation sequencing in Central China

目的:分析中国中部女性遗传性乳腺癌患者BRCA1/2基因遗传变异情况,探究中国人群乳腺癌易感基因BRCA1/2的遗传变异热点,为临床乳腺癌风险评估提出可靠依据。方法:对乳甲外科收治的具有乳腺癌家族史的女性患者62例,无家族史正常女性志愿者60例,利用Life Tech Ion Proton高通量测序技术对BRCA1/2基因进行测序分析,并用sanger测序法验证。结果:在62例有家族史乳腺癌患者中,BRCA1基因突变率为25.8%(16/62),BRCA2基因突变率为33.9%(21/62),BRCA1/2有害变异率为11.3%(7/62)。乳腺癌家族史患者组与正常组对比分析,家族史乳腺癌患者组BRCA1/2基因变异率(45.2%)显著高于正常对照组(31.7%)。通过家系分析和数据比对发现BRCA1c.4986+1G>T和BRCA2 5773C>T为中国人群遗传性乳腺癌有害变异。结论:家族遗传性乳腺癌患者BRCA1/2基因变异率显著高于正常人群。通过家系遗传分析并利用高通量测序技术可以有效地筛选出乳腺癌BRCA1/2基因的有害变异,为乳腺癌的风险评估提供可靠的临床依据。

Objective To analyze the BRCA1/2 gene variations of women patients with hereditary breast cancer in Central China and investigate the mutation hotspots of breast cancer susceptibility gene BRCA1/2 in Chinese population to provide reliable evidencefor the clinical assessment of breast cancer risk. Methods 62 cases of female hereditary breast cancer patients and 60 cases of normal female volunteers witboutfamily history of breast cancer from Renmin Hospital of Wuhan University participated in this study between June 2013 and June 2016. All participants received genetic counseling and BRCA1/2 genetic testing by next-generation sequencing （NGS） of Life Tech Ion Proton,and all mutations were confirmed with Sanger sequencing. Results The prevalence of BRCA mutations in the group of hereditary breast cancer was as follows： 25.8% for patients with the BRCA1 gene variations, 33.9% for the patients with the BRCA2 gene variations, and 11.3% for the patients with the deleterious variations of BRCA1/2. Compared with normal female volunteersgroup, the BRCA1/2 gene mutation rate （45.2%） of the group of hereditary breast cancer was significantly higher than the control group （31.7%）. It was confirmed that BRCAlc.4986＋1G〉T and BRCA2 5773C 〉T were deleterious mutation of hereditary breast cancer in Chinese population by pedigree and data analysis. Conclusions BRCA1/2 gene mutation rate of patients with hereditary breast cancer was significantly higher than the normal population, which can propose reliable evidence for the clinical assessment of breast cancer risk by the technology of NGS and pedigree analysis.