期刊
WORLD JOURNAL OF GASTROENTEROLOGY
卷 9, 期 4, 页码 655-659出版社
W J G PRESS
DOI: 10.3748/wjg.v9.i4.655
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AIM: To appraise the correlation of mutation and methylation of hMSH1 with microsatellite instability (MSI) in gastric cancers. METHODS: Mutation of hMLH1 was detected by Two-dimensional electrophoresis (Two-D) and DNA sequencing; 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 mutation and methylatlon of hMLH1 promoter and MSI. Three mutations were found, two of them were caused by a single by substitution and one was caused by a 2 by substitution, which displayed similar Two-D band pattern. Methylation of hMLH1 promoter was detected in 11(16.2%) gastric cancer. By using five MSI markers, MSI in at least one locus was detected in 17/68(25%) of the tumors analyzed. Three hMLH1 mutations were all detected in MSI-H (greater than or equal to 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 frequency of hMLH1 in MSI-H (87.5%, 7/8) was significantly higher than that in MSI-L (11.1%, 1/9) or MSS (5.9%, 3/51) (P < 0.01-0.001), but no difference was found between MSI-L and MSS (P > 0.05). CONCLUSION: Both mutation and methylation of hMLH1 are involved in the MSI pathway but not related to the LOH pathway in gastric carcinogenesis.
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