摘要
目的研究乳腺癌易感基因BRCA1、BRCA2、TP53、PTEN在中国乳腺癌患者中发生胚系突变的情况。方法本研究为探索性研究,选择2016年1月至2018年8月就诊于北京大学人民医院乳腺外科的女性乳腺癌患者128例。其中散发乳腺癌患者44例,具有遗传性乳腺癌高危因素的乳腺癌患者84例。应用二代测序技术对患者进行BRCA1、BRCA2、TP53及PTEN 4个基因的胚系突变情况进行检测。χ^2检验分析4种基因突变携带率在散发病例及具有遗传性高危因素的乳腺癌患者之间的分布。按照患者临床特点(有无家族史、是否为三阴型乳腺癌、年龄及是否为双侧乳腺癌)进行分组,其中有明确乳腺癌家族史42例,三阴型乳腺癌34例,早发性乳腺癌33例,双侧乳腺癌7例,Fisher确切概率检验比较BRCA1/2基因致病突变与遗传性高危因素乳腺癌患者临床特征之间的关系。结果128例乳腺癌患者中,检测到BRCA1/2胚系突变30例,其中致病突变13例,3例新发突变,BRCA1:c.4760C>G、BRCA2:c.4413_4414del和BRCA2:c.6482_6485del可能为中国人群特有突变。TP53突变3例,其中1例致病突变。3例突变均为早发乳腺癌。5例PTEN突变,其中3例致病突变。在84例具有遗传性高危因素的乳腺癌患者中4种易感基因突变的患者携带率40.5%(34/84),致病突变率15.4(13/84)。44例散发病例中,携带突变率为9%(4/44)。致病突变率为6.8%(3/44)。乳腺癌易感基因在具有遗传性高风险因素的乳腺癌患者携带率更高,与散发病例人群差异存在统计学意义(P<0.001)。BRCA1/2突变在具有遗传性高风险因素的乳腺癌患者各分组中差异均无统计学意义。结论乳腺癌易感基因胚系突变检测在乳腺癌风险预测、预后评价等方面具有重要意义。
Objective To investigate germline mutation of breast cancer susceptibility genes BRCA1/2,TP53 and PTEN in Chinese breast cancer patients.MethodsAll of128 female breast cancer patients in Peking University People′s Hospital from January 2016 to August 2018 were selected as objects.Among them,44 cases were sporadic breast cancer and 84 werebreast cancer patients with genetic high risks.Germline mutations of BRCA1,BRCA2,TP53 and PTENwere detected by NGS.χ^2 test was used to analyze the difference of pathogenic mutation rates between sporadic breast cancer group and breast cancer with high genetic risks.Groups were divided according to the clinical features of the patients(family history,triple-negative breast cancer,age and bilateral breast cancer).Among them,there were 42 cases with family history of breast cancer,34 cases of triple-negative breast cancer,33 cases of early-onset breast cancer and 7 cases of bilateral breast cancer.Fisher′s exact probability test compared the relationship between pathogenic mutations of BRCA1/2 gene and clinical characteristics of breast cancer patients with hereditary risk factors.ResultsIn 128 cases of breast cancer,30 germline mutations of BRCA1/2 were detected,including 13 pathogenic mutations and 3 newly discovered mutations(BRCA1:c.4760C>G,BRCA2:c.4413_4414del and BRCA2:c.6482_6485del).The new mutations may be unique mutations of Chinese population.There were 3 cases of TP53 mutations,including 1 pathogenic mutation.All of the 3 mutations were found in early-onset breast cancer.Germline mutation of T53 has important detection significance for early-onset hereditary breast cancer.There were 5 cases of PTEN mutations,including 3 pathogenic mutations.Among 84 breast cancer patients with genetic high risks,the carry mutation rate was 40.5%(34/84)and the pathogenic mutation rate was 15.4(13/84).Among 44 sporadic cases,the carry mutation rate was 9%(4/44).The pathogenic mutation rate was 6.8%(3/44).Breast cancer susceptibility genes were carried at a higher rate in breast cance
作者
刘畅
马寅婷
卓钟灵
谢菲
孙媛媛
龙彦
王辉
赵晓涛
Liu Chang;Ma Yinting;Zhuo Zhongling;Xie Fei;Sun Yuanyuan;Long Yan;Wang Hui;Zhao Xiaotao(Peking Unirersity People's Hospital,Beijing 100044,China)
出处
《中华检验医学杂志》
CAS
CSCD
北大核心
2019年第2期98-103,共6页
Chinese Journal of Laboratory Medicine
基金
北京市自然科学基金(7172225).
