title: Genetic and epigenetic alterations of tumor suppressor and tumor-related genes in gastric cancer.
abstract: Both genetic and epigenetic alterations of tumor suppressor and tumor-related genes involved in the pathogenesis of gastric cancer are reviewed here, and molecular pathways of gastric carcinogenesis are proposed. Gastric carcinomas are believed to evolve from native gastric mucosa or intestinal metaplastic mucosa that undergoes genetic and epigenetic alterations involving either the suppressor pathway (defects in tumor suppressor genes) or mutator pathway (defects in DNA mismatch repair genes). Methylation of E-cadherin in native gastric mucosa results in undifferentiated carcinomas (suppressor pathway), while methylation of hMLHI results in differentiated foveolar-type carcinomas (mutator pathway). The majority of differentiated gastric carcinomas however, arise from intestinal metaplastic mucosa and exhibit structural alterations of tumor suppressor genes, especially p53. They appear to be related to chronic injury, perhaps due to Helicobacter pylori infection. Approximately 20% of differentiated carcinomas (ordinary-type) have evidence of mutator pathway tumorigenesis. Mutations of E-cadherin are mainly involved in the progression of differentiated carcinomas to undifferentiated tumors. The molecular pathways of gastric carcinogenesis depend on the histological background, and gastric carcinomas show distinct biological behaviors as a result of discernible cellular genetic and epigenetic alterations.
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, Japan. gtamura@med.id.yamagata-u.ac.jp
authors.forename: G
authors.initials: G
authors.lastname: Tamura
mesh_terms: D000818:Animals; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*