原发性胃癌中MRE11基因的突变筛查

目的:研究染色体不稳定性相关基因MRE11(meiotic recombination 11 homolog A)突变与原发性胃癌的相关性。方法:收集27例原发性胃癌病人的胃癌组织和对应的正常胃黏膜组织,并通过显微切割方法从胃癌组织中获取较纯胃癌细胞。设计扩增MRE11基因外显子的引物共20对,采用PCR产物直接测序方法在胃癌细胞和对应正常胃黏膜组织中对MRE11基因编码区进行突变检测,并运用CGH方法对存在突变的胃癌细胞进行染色体分析。结果:在27例原发性胃癌中,4例存在MRE11基因共4个体细胞水平的错义突变,其中3例为肠型胃癌。CGH显示该4例胃癌均存在5个以上基因组片断的获得或丢失事件。结论:MRE11基因突变可能在某些原发性胃癌的发生发展中起着重要作用,尤其是显示染色体不稳定性的肠型胃癌。

MRE11 gene mutation in primary gastric carcinomas

Objective To investigate the role of the chromosomal instability (CIN)-related gene MRE11(meiotic recombination 11 homolg A) mutations in primary gastric carcinomas. Methods Mutations of MRE11 gene coding sequence were detected by PCR and DNA sequencing in cancerous lesions and their corresponding noncancerous tissues from 27 gastric cancer patients. Comparative Genomic Hybridization (CGH) was further performed if MRE11 mutation was found. Results Four somatic missense mutations of MRE11 gene were identified in 4 gastric carcinoma cases, which were C1328C/A (A390G), C2050C/A (P631T) and G2057A (R633Q). Among these patients, three of them belonged to the intestinal type. Changing of DNA sequence copy number involving over 5 regions of the genome was detected by CGH analysis. Conclusions Mutations of MRE11 may play a role in gastric carcinogenesis, especially in the intestinal-type with CIN.