乳腺癌BRCA1基因突变及其蛋白表达研究

目的 :探讨散发性乳腺癌的BRCA1基因突变及其蛋白表达与临床病理因素的关系。方法 :收集乳腺癌患者外周血 10 2份、新鲜肿瘤组织 30份 ,分别采用PCR SSCP、DHPLC和基因测序对BRCA1基因第 2、8- 1、8- 2和 2 0外显子进行突变检测 ;对 10 4例肿瘤组织切片进行免疫组化染色标记BRCA1蛋白表达 ,分析免疫组化结果与临床资料的关系。结果 :分别在外显子 8- 1和 8- 2的 2 882 1和 2 8978位点上发现 3例碱基缺失和置换现象。BRCA1蛋白在乳腺癌组织中表达下降 ,且与患者生存状态有关。结论 :在中国散发性乳腺癌患者中BRCA1基因外显子 2、8和 2 0的突变率较低 (2 3% ) ,可以认为在普通中国人群中乳腺癌的发生与该部分碱基序列突变的关系不大 ,但BRCA1蛋白低表达乳腺癌患者复发的危险性增大

Study on BRCA1 Mutation and Expression in Breast Cancer

Objective To investigate the mutation and the relationship between protein expression of BRCA1 and the clinical pathological data in Chinese patients with breast cancer.Methods Denaturing highperformance liquid chromatography(DHPLC) and single stranded conformation polymophism(SSCP) were used to detect the mutations of exons 2,8-1,8-2 and 20 of BRCA1 in 132 sporadic breast cancer cases,and BRCA1 protein expression were determined by immunohistochemical method in 104 cases.Results Mutations of 1 case at 28821 of exon 8-1 and 2 cases at 28978 of exon 8-2 were found,the level of BRCA1 protein expression was associated with life status in breast cancer.Conclusion As the mutation rate was only 2 3%,exons 2,8 and 20 of BRCA1 can hardly account for the occurrence of sporadic breast cancer cases in China,while the patient with low expression of BRCA1 protein may be liable to recurrence.