一个汉族乳腺癌家族BRCA1 c.2013_2014insGT的检出与变异表型分析  

Detection of a BRCA1 c.2013_2014ins GT variant an ethnic Han Chinese pedigree affected with breast cancer

作　　者：齐攀[1] 高琳琳 和小颖 倪悦涵 徐升[1] 麦雪莹 张桂凌[1] 刘玉霞[1] 郭予[1] 周勇[1] 胡庆涛 Qi Pan;Gao Linlin;He Xiaoying;Ni Yuehan;Xu Sheng;Mai Xueying;Zhang Guiling;Liu Yuxia;Guo Yu;Zhou Yong;Hu Qingtao(Department of Head,Neck and Breast Surgery,Xinxiang Central Hospital,Henan 453000,China;Beijing Institute of Biological Sciences,Beijing 102200,China)

机构地区：[1]新乡市中心医院头颈乳腺科,河南453000 [2]北京生命科学研究所,102206

出　　处：《中华医学遗传学杂志》2020年第4期415-418,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(31701135);河南省医学科技攻关计划(20180209727)。

摘　　要：目的筛查一个乳腺癌家系的致病变异。方法应用靶向外显子捕获测序技术检测8位家系成员121个遗传性癌症相关基因,分析变异与疾病共分离情况得到候选致病位点,然后采用Sanger测序和克隆测序在所有9位家系成员中对候选致病位点验证。结果本家系中6位确诊乳腺癌的家系成员均携带BRCA1基因c.2013_2014insGT杂合变异,未患乳腺癌的女性不携带该变异。千人基因组计划数据库和外显子集成联合数据库(The Exome Aggregation Consortium,ExAC)均未收录该变异,开放读码框预测该变异导致蛋白翻译提前终止形成截短的BRCA1蛋白。结论BRCA1基因c.2013_2014insGT变异为该乳腺癌家系的致病原因。Objective To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer.Methods The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes.Candidate variants were selected by analysis of their type,frequency in population,and segregation with the phenotype.Candidate variant was verified by Sanger sequencing and TA cloning.Results A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females.The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium(ExAC)database.The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein.Conclusion The BRCA1c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.

关 键 词：乳腺癌 家族性遗传 BRCA1基因 捕获测序 

分 类 号：R737[医药卫生—肿瘤]