32例三阴性乳腺癌患者易感基因胚系突变分析  

Analysis of germline mutation of 32 patients with triple negative breast cancer by whole exome sequencing

作　　者：隆建萍[1] 闫有圣 杨涛[1] 马秀芬[1] 毛红岩[1] 张庆华[1] 独晓燕[1] 高华方 LONG Jianping;YAN Yousheng;YANG Tao;MA Xiufen;MAO Hongyan;DU Xiaoyan;GAO Huafang(Gansu Provincial Maternity and Child Health Care Hospital,Lanzhou,Gansu Province,730050;National Research Institute for Family Planning)

机构地区：[1]甘肃省妇幼保健院,兰州730050 [2]国家卫健委科学技术研究所

出　　处：《中国计划生育学杂志》2021年第1期175-180,共6页Chinese Journal of Family Planning

基　　金：甘肃省自然科学基金(17JR5RA030)。

摘　　要：目的:应用全外显子测序技术初步探讨三阴性乳腺癌(TNBC)患者易感基因突变情况。方法:收集本院就诊的32例TNBC患者,均经临床手术病理确诊。采集患者外周血提取基因组DNA进行全外显子组测序,通过生物信息学分析筛选与乳腺肿瘤相关的易感基因变异。结果:32例TNBC患者中14例检测到BRCA1/2罕见变异,明确致病性或可疑致病变异6例,突变携带频率为18.8%。其中BRCA1:c.5468-1_5474del和c.4749_4750del是较常见的突变;BRCA2:c.6027A>C为新的变异;BRCA2:c.3794G>T、c.7901T>A,BRCA1:c.4616T>C首次在中国人群中发现。除了BRCA1/2变异外,还检测到83个乳腺肿瘤易感基因变异,每个患者携带2.6个变异。2个以上患者携带的乳腺癌易感基因包括ALK、APC、CDH1、PTCH2、RB1CC1、RAD51D、RAD54L、TSC1等。结论:BRCA1/2是TNBC患者最重要的易感基因,其他与DNA损伤修复相关的基因突变可能与TNBC患者的表型有一定的相关性。Objective:To investigate the susceptibility gene mutation of patients with triple negative breast cancer(TNBC)by whole exome sequencing(WES).Method:32 patients with TNBC admitted to Gansu provincial maternity and child health care hospital were confirmed by clinical surgery and pathology.Genomic DNA was extracted from the patients'peripheral blood for WES,and the sequencing data were analyzed by bioinformatics to screen for susceptibility gene variations related to breast tumors.Results:Among the 32 patients,the rare variants of BRCA1/2 were detected in 14 cases,which included 6 cases with pathogenic variants and likely pathogenic variants,with frequency of 18.8%.Among them,BRCA1:C.5468-1_5474del and C.4749_4750del were the common mutations,BRCA2:c.6027A>C was novel variant,and BRCA2:c.3794G>T、c.7901T>A,BRCA1:c.4616T>C were the first reported in Chinese patients.In addition to BRCA1/2,83 breast tumor susceptibility gene variants were detected in 32 cases by WES,with approximately 2.6 variants per patient.The breast cancer susceptibility genes carried by more than 2 patients include:ALK,APC,CDH1,PTCH2,RB1CC1,RAD51D,RAD54L,TSC1,etc.Conclusion:BRCA1/2 is the most prevalent susceptibility gene of patients with TNBC,and other gene variants related to DNA damage repair may be correlated with the phenotype of TNBC patients.

关 键 词：三阴性乳腺癌 高通量测序 全外显子组测序 BRCA1/2 

分 类 号：R737.9[医药卫生—肿瘤]