HER2阳性乳腺癌ERBB3基因E928G点突变功能的初步研究  

Preliminary Study of HER2 Positive Breast Cancer Cell with ERBB3 Gene E928G Mutation

作　　者：韦光楠 廖宁 陈博 WEI Guangnan;LIAO Ning;CHEN Bo(South China University of Technology Medical School,Guangzhou 510006,China;Department of Breast Surgery,Guangdong Academy of Medical Sciences/Guangdong Provincial People′s Hospital,Guangzhou 510080,China)

机构地区：[1]华南理工大学医学院,广州510006 [2]广东省人民医院广东省医学科学院乳腺外科,广州510080

出　　处：《医学综述》2022年第7期1441-1445,共5页Medical Recapitulate

摘　　要：目的通过二代基因测序检测乳腺癌人表皮生长因子受体(HER)家族的变异情况,并对检测到ERBB3点突变人群进行分析,寻找具有临床意义的位点。方法收集2017年6月至2019年5月于广东省人民医院就诊的384例乳腺癌患者的原发肿瘤组织,采用二代基因测序技术分析HER家族的变异情况,通过生物信息学软件分析ERBB3突变位点是否为有害位点,Western blot验证ERBB3点突变对细胞功能的影响。结果在384例患者中有13例患者发现ERBB3变异,主要的变异类型为错义突变。通过生物信息学软件的计算显示,D297Y、T355I、E928G、E1261A、L431F、P583S、R667L、D297H、R678W位点突变可能为有害突变。ERBB3基因E928G突变的HER2阳性乳腺癌细胞磷酸化蛋白激酶B(PKB/Akt)水平显著升高。结论ERBB3基因E928G突变的HER2阳性乳腺癌细胞可能存在下游磷脂酰肌醇-3-激酶/Akt信号通路异常激活,可能与抗HER2靶向治疗耐药相关。Objective To investigate variation of human epidermal growth factor receptor(HER)family in breast cancer patients by the next generation sequencing(NGS),and the population with ERBB3 point mutation was analyzed to find the clinically significant loci.Methods Primary tumor tissues of 384 breast cancer patients treated in Guangdong Provincial People′s Hospital from Jun.2017 to May 2019 were collected.The NGS technology was used to analyze the variation of HER family,and bioinformatics software was used to analyze whether the ERBB3 mutation site was harmful.Western blot was used to verify the effect of ERBB3 point mutation on cell function.Results Among the 384 breast cancer patients,there were 13 ERBB3 mutation cases discovered,and the main mutation type was missense mutation.Bioinformatics software analysis showed ERBB3 mutations at the points of D297Y,T355I,E928G,E1261A,L431F,P583S,R667L,D297H and R678W were probably damaging.The level of phosphorylated protein kinase B(PKB/Akt)in HER2 positive breast cancer cells with ERBB3 gene E928G mutation was significantly elevated.Conclusion The HER2 positive breast cancer cells with ERBB3 gene E928G mutation may have abnormal activation of downstream phosphatidylinositol-3-kinase/Akt signaling pathway,which may be associated with resistance to HER2 targeted therapy.

关 键 词：人表皮生长因子受体2阳性乳腺癌 二代基因测序 定点突变 ERBB3 E928G 

分 类 号：R737.9[医药卫生—肿瘤]