乳腺癌多通路基因检测及突变情况分析  

Detection of multi-pathway genes and analysis of gene mutations in breast cancer

作　　者：刘芃菲 卓钟灵 刘畅[1] 陈彦丽 杨子瑶 赵晓涛[1] Liu Pengfei;Zhuo Zhongling;Liu Chang;Chen Yanli;Yang Ziyao;Zhao Xiaotao(Department of Laboratory Medicine,Peking University People′s Hospital,Beijing 100044,China)

机构地区：[1]北京大学人民医院检验科,北京100044

出　　处：《中华检验医学杂志》2021年第5期394-401,共8页Chinese Journal of Laboratory Medicine

基　　金：北京市自然科学基金(7172225)。

摘　　要：目的研究中国女性乳腺癌患者多通路胚系基因突变分布及其与临床病理特征的相关性,丰富中国人群乳腺癌胚系基因突变数据库,为乳腺癌靶向药的应用提供实验室依据。方法收集2017年1月至2019年7月北京大学人民医院乳腺外科经病理诊断确诊的148例乳腺癌女性患者的全血样本,发病年龄24~80岁。应用二代测序技术检测患者HR、MMR、BER、KDR通路相关基因的胚系突变情况,进行致病性判读,筛选出致病、可能致病和致病意义未明的突变,分析患者发病年龄、luminal分型、肿瘤大小、肿瘤转移情况、家族史等临床病理特征,采用χ2检验和Fisher确切概率检验研究不同通路基因突变与临床病理特征的相关性。结果148例乳腺癌患者中,69例携带HR通路基因突变(包括致病、可能致病、致病意义不明3类突变),16例携带MMR通路基因突变,6例携带BER通路基因突变,8例携带KDR通路基因突变。HR通路的ATM基因突变与乳腺癌luminal分型呈相关性趋势(P=0.059),突变倾向于发生在HER2过表达型乳腺癌患者中。MMR通路的PMS2突变与肿瘤大小呈相关性趋势(P=0.060),突变倾向于发生在肿瘤直径>50 mm的患者中。KDR基因突变与乳腺癌luminal分型和家族史具有相关性(P=0.002,P=0.024)。结论中国女性乳腺癌人群BER、KDR、MMR、HR通路的基因突变检出频率依次升高。ATM、PMS2和KDR基因的胚系突变可能参与了中国女性乳腺癌的发生发展。乳腺癌多通路基因检测可为PARP抑制剂、曲妥珠单抗等靶向药物的使用提供实验室依据。Objective To investigate the germline mutation status in multi-pathway in Chinese female breast cancer patients and explore their correlation with clinicopathological characteristics.Aim to enrich the database of breast cancer germline gene mutations in Chinese population and provide laboratory evidence for the application of breast cancer targeted drugs.Methods From January 2017 to July 2019,whole blood samples were collected from 148 women(age of onset concentrated in the 24~80 years old)diagnosed pathologically with breast cancer in the Department of breast surgery,Peking University People′s Hospital.Germline mutations in HR,MMR,BER,and KDR pathway related genes were detected by next-generation sequencing.The pathogenicity interpretation was performed,and pathogenic,likely pathogenic,and mutations of uncertain significance were screened.The clinicopathological characteristics including age at the onset,luminal typing,tumor size,metastasis,and family history were analyzed,and the correlation between mutations in different pathway genes and clinicopathological characteristics was analyzed by the Chi-squared test and Fisher′s exact probability test.Results Among the 148 patients,there were 69 cases of HR mutations(including three types of mutations,including pathogenic,likely pathogenic and uncertain significance),16 cases of MMR mutations,6 cases of BER mutations and 8 cases of KDR mutation.ATM mutations in the HR pathway were associated with luminal typing(P=0.054),and patients with HER2+breast cancer were more likely to carry ATM mutations.PMS2 mutations in the MMR pathway were correlated with tumor size(P=0.060),and patients with tumor size>50 mm were more likely to carry PMS2 mutations.KDR mutations was significantly correlated with luminal typing and family history.(P=0.021,P=0.024).Conclusion The mutation frequency in BER,KDR,MMR and HR pathways in Chinese breast cancer patients increased successively.Germline mutations in ATM,PMS2 and KDR genes may be involved in the development of breast cancer in th

关 键 词：乳腺肿瘤 二代测序 DNA损伤修复 基因突变 

分 类 号：R737.9[医药卫生—肿瘤]