Objective: To study the correlation of the methylation of the promoters of hMLH1 and hMSH2 with microsatellite instability (MSI) in the tissues of gastric carcinomas. Methods: A total of 68 sporadic cases of gastric c...Objective: To study the correlation of the methylation of the promoters of hMLH1 and hMSH2 with microsatellite instability (MSI) in the tissues of gastric carcinomas. Methods: A total of 68 sporadic cases of gastric carcinoma were studied. Ten specimens of normal gastric mucosa served as control. Methylation of hMLHl and hMSH2 was observed with methylation-specific PCR, and MSI analyzed with PCR-based techniques. Results: No methylation of hMLHl and hMSH2 was found in 10 specimens of normal gastric mucosa. Methylation of hMLHl was detected in 11 cases (16. 2%) of gastric cancers and MSI in at least one locus was found in 17 cases (25%) of the 68 with aid of 5 microsatellite markers, in which eight were MSI-H (≥2loci showed instability) nine MSI-L (only one locus showed instability), and fifty-one were MSS (no instability at any marker). The frequency of methylation was significantly high in MSI-H (87. 5%) than in MSI-L (11.1%) and MSS (5. 9%). CP<0. 01 - 0. 001) but there was no difference of methylation frequency between the cases with MSI-L and those with MSS. Conclusion: Methylation of hMLHl promoter is involved to the MSI pathway but not to the loss of heterozygosity (LOH) pathway in gastric carcinogenesis.展开更多
基金Supported by National Natural Science Foundation of China (No. 30070043) , and "the Tenth five-year Plan"Scientific Research Foundation of Chinese PLA (No. 01Z075)
文摘Objective: To study the correlation of the methylation of the promoters of hMLH1 and hMSH2 with microsatellite instability (MSI) in the tissues of gastric carcinomas. Methods: A total of 68 sporadic cases of gastric carcinoma were studied. Ten specimens of normal gastric mucosa served as control. Methylation of hMLHl and hMSH2 was observed with methylation-specific PCR, and MSI analyzed with PCR-based techniques. Results: No methylation of hMLHl and hMSH2 was found in 10 specimens of normal gastric mucosa. Methylation of hMLHl was detected in 11 cases (16. 2%) of gastric cancers and MSI in at least one locus was found in 17 cases (25%) of the 68 with aid of 5 microsatellite markers, in which eight were MSI-H (≥2loci showed instability) nine MSI-L (only one locus showed instability), and fifty-one were MSS (no instability at any marker). The frequency of methylation was significantly high in MSI-H (87. 5%) than in MSI-L (11.1%) and MSS (5. 9%). CP<0. 01 - 0. 001) but there was no difference of methylation frequency between the cases with MSI-L and those with MSS. Conclusion: Methylation of hMLHl promoter is involved to the MSI pathway but not to the loss of heterozygosity (LOH) pathway in gastric carcinogenesis.
