肿瘤细胞膜蛋白体细胞突变分析  

Analysis of somatic mutations in membrane proteins of tumor cells

作　　者：吴姗姗[1] 周展[1] 陈枢青[1] 

机构地区：[1]浙江大学药学院/浙江省抗肿瘤药物临床前研究重点实验室,浙江杭州310058

出　　处：《中国生化药物杂志》2015年第11期1-4,10,共5页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然科学基金重点项目(81430081);浙江省自然科学基金面上项目(LY15C06001)

摘　　要：目的筛选肿瘤细胞特异性膜蛋白胞外突变(特异性膜表面蛋白突变),以期寻找癌症精准医疗的作用靶点。方法收集7042个肿瘤样本的体细胞突变信息,通过对体细胞突变位点进行基因定位分析,筛选出全部特异性膜蛋白胞外突变,并统计分析这些突变的整体分布情况,鉴定特异性膜蛋白胞外突变频率较高的基因、突变位点以及肿瘤类型。结果对7042个肿瘤样本的4938362个体细胞突变,共筛选出97193个特异性膜蛋白胞外突变,统计分析结果显示这些突变涉及4347个基因,包括65532个基因位点。进一步分析鉴定出发生特异性膜蛋白胞外突变频率较高的5个基因(MUC16、LRP1B、CSMD3、RYR2、USH2A),1个突变位点(17∶37868208)以及6个肿瘤类型(结直肠癌、黑素瘤、子宫癌、脑胶质瘤、肺癌和胃癌)。结论建立了特异性膜蛋白胞外突变信息库,并得到了该类突变的整体分布情况,为寻找癌症精准医疗的作用靶点提供了信息参考。Objective To screen specific mutations on extracellular regions of membrane proteins（ extracellular membrane protein mutations） in tumor cells and provide the reference information for target searching in cancer precision medicine. Methods Somatic mutations on extracellular regions of membrane proteins of 7042 tumor samples were collected to screen all specific extracellular membrane protein mutations,and the overall distribution of these mutations were obtained by statistical analysis. Genes,gene site and cancer types occured high frequency of extracellular membrane protein mutations were identified. Results 97193 specific extracellular membrane protein mutations were obtained from 4938362 somatic mutations in 7042 tumor samples（ 30 cancer types）,the statistical analysis showed that 4347 genes and 65532 sites were involved in these specific mutations. The study further analyzed five genes（ MUC16、LRP1B、CSMD3、RYR2、USH2A）,one site（ 17 ∶37868208） and six cancer types（ including colorectal cancer,melanoma,uterine cancer,brain lower grade glioma,lung adenocarcinoma and stomach adenocarcinoma） which occured high frequency of extracellular membrane protein mutations. Conclusion An information library of specific mutations on extracellular regions of membrane proteins was established and the distribution of these specific mutations was obtained which can provide reference information for target detection in targeted cancer therapy and immunological therapy.

关 键 词：癌症精准医疗 作用靶点 体细胞突变 特异性膜蛋白胞外突变 

分 类 号：R730.1[医药卫生—肿瘤]