多种恶性肿瘤p21基因启动子及编码区点突变的检测  

Detection of point mutations in promoter and coding sequence of p21 gene in a variety of human malignancies

作　　者：黄倩[1] 陶勇浩[1] 

机构地区：[1]上海市第一人民医院,200080

出　　处：《中华医学遗传学杂志》2000年第3期169-172,共4页Chinese Journal of Medical Genetics

摘　　要：目的　探讨 p2 1基因点突变是否与恶性肿瘤的发生发展过程有关 ,特别是与那些没有 p5 3基因突变的恶性肿瘤发病的关系。方法　结合 SSCP分析及 DNA序列测定技术 ,检测 34 6例 9种不同组织学类型的恶性肿瘤 p2 1基因的启动子和主要的编码区。结果　 34 6例恶性肿瘤的 p2 1基因启动子未检测到突变 ,但在 P5 3蛋白结合位点上游及下游处存在多态性变异。仅 1例膀胱癌有一杂合性 44 bp缺失突变。此外 ,在编码区内还发现了 1个多态性位点 ,以及 4种少见的 DNA序列变异。结论　原发恶性肿瘤中 p2Objective p21 is a general inhibitor of cyclin dependent kinases which leads cells through restriction point of cell cycle. Since p21 has been identified to be a mediator of p53 tumor suppressor activity and directly up regulated by p53, this study was designed to investigate whether mutations in promoter or coding sequence of p21 were associated with development or progress of tumor.Methods A 2.4 kb DNA fragment, containing essential promoter, was amplified and sequenced. Furthermore, 346 DNA samples from 9 different types of primary tumors were examined for point mutations in promoter and coding sequence of p21 gene by using SSCP analysis and direct sequencing.Results Heterozygous or homozygous G to A transition at 5bp upstream and C to A transversion at 160bp downstream of p53 binding site were found. A 44bp heterozygous deletion was detected in a bladder cancer, which started at codon 34 and resulted in frameshift and a premature stop codon downstream. The most abundant variants in coding sequence of p21 gene were a C to A transversion at codon 31 which resulted in Ser to Arg and had been identified being polymophism. In addition, four rare variants in coding sequence were also found.Conclusion The evidence from this study indicates that mutation in either promoter or coding sequence of p21 gene is rare in a variety of human malignancies.

关 键 词：P21基因 启动子 点突变 恶性肿瘤 

分 类 号：R73-3[医药卫生—肿瘤]