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首页> 外文期刊>World Journal of Gastroenterology >Mutation and methylation of hMLH1 in gastric carcinomas with microsatellite instability
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Mutation and methylation of hMLH1 in gastric carcinomas with microsatellite instability

机译：微卫星不稳定性胃癌中hMLH1的突变和甲基化

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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 methylation of hMLH1 promoter and MSI. Three mutations were found, two of them were caused by a single bp substitution and one was caused by a 2 bp 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 (≥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.
机译：目的：评估胃癌中hMSH1的突变和甲基化与微卫星不稳定性（MSI）的相关性。方法：采用二维电泳和DNA测序技术检测hMLH1突变。用甲基化特异性PCR检测hMLH1启动子的甲基化；通过基于PCR的方法分析MSI。结果：研究了68例散发性胃癌的hMLH1启动子和MSI的突变和甲基化。发现了三个突变，其中两个是由单个bp取代引起的，一个是由2 bp取代引起的，显示了相似的二维条带模式。在11（16.2％）胃癌中检测到hMLH1启动子的甲基化。通过使用五个MSI标记，在所分析的17/68（25％）的肿瘤中至少一个基因座中检测到MSI。在MSI-H（≥2个基因座，n = 8）中均检测到三个hMLH1突变，但在MSI-L（仅一个基因座，n = 9）或MSS（肿瘤缺乏MSI或稳定，n = 51）中未发现突变）。 MSI-H中hMLH1的甲基化频率（87.5％，7/8）显着高于MSI-L（11.1％，1/9）或MSS（5.9％，3/51）（P <0.01-0.001） ，但在MSI-L和MSS之间没有发现差异（P> 0.05）。结论：hMLH1的突变和甲基化均参与MSI途径，但与胃癌发生过程中的LOH途径无关。

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