Relationship between mismatching repair gene hMLH1 mutation and promoter methylation and genetic instability in gastric cancer / 中华消化杂志

ABSTRACT

Objective To evaluate the relationship between hMLH1 mutation and promoter methylation and genetic instability in gastric carcinomas. Methods hMLH1 mutation was measured by two dimentional DNA electrophoresis and DNA sequencing. The methylation of hMLH1 promoter was measured with methylation specific PCR. MSI was analyzed by PCR based methods. Results Sixty eight cases of sporadic gastric carcinoma were studied for hMLH1 mutation and promoter methylation. hMLH1 mutaions were detected in three cases (4.4%) of gastric cancer. No association was observed between hMLH1 mutation and tumor size, differentiation, histological type, depth of invasion, metastasis or stages. Methylation of hMLH1 promoter was detected in 11 cases (16.2%) of gastric cancer. By using five microsatellite markers, MSI in at least one locus was detected in 17 of 68 (25%) cases of the tumors analyzed. hMLH1 mutations were all detected in MSI H(≥2 loci, n =8), but no mutation was found in MSI L (only one locus, n =9) or MSS (tumor lacking MSI or stable, n =51). Methylation frequence of hMLH1 in MSI H was significantly higher than that in MSI L or MSS ( P 0.05). Conclusion hMLH1 mutation and promoter methylation may be involved in MSI pathway in gastric cancer.