Molecular biology of gastric cancer.
Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic type. Decreased expression of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at the DCC locus are preferentially associated with well differentiated gastric cancer. Moreover, LOH on chromosome 1q is involved in the progression of well differentiated cancer. Precancerous lesions, including hyperplastic polyp, intestinal metaplasia, and adenoma, share genetic changes found in well differentiated cancers. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis of the poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated or scirrhous carcinoma. Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is implicated in the morphogenesis of two types of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
Tahara
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Department of Pathology, Hiroshima University School of Medicine, Japan.
D000230:Adenocarcinoma / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D016158:Genes, p53; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D009154:Mutation; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*
D015815:Cell Adhesion Molecules; D016207:Cytokines; D006133:Growth Substances; D020794:Receptor Protein-Tyrosine Kinases