Analysis of molecular mechanism of premalignant lesion of the stomach using genomic instability and new mucin gene.

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1) High frequency of the genomic instability (microsatellite instability, MSI) was found in well-differentiated adenocarcinoma of the stomach. Most of the intestinal metaplasia lesion which was accompanied with well-differentiated adenocarcinoma showed positivity for MSI.Moveover, hypermethylation of the promotor lesion of hMLH1 gene was observed in MSI-positive adenocarcinoma. Further study will be needed to analyze the association between MSI status and hypermethylation of the DNA repair genes and other related genes.2) New mucin gene A3D4 was expressed in the lesion of intestinal metaplasia of the adenocarcinoma of the stomach. This product was negative for "normal" intestinal metaplasia lesion.3) Methylation has systemically been investigated in the lesion of the intestinal metaplasia and many genes were found to show abnormal pattern of methylation, suggesting the important role of methylation to the premalignant status of the stomach cancer.