J Korean Med Assoc.  2010 Apr;53(4):270-282. 10.5124/jkma.2010.53.4.270.

Molecular Pathogenesis of Gastric Cancer

• Park WS

• KMID: 2188286
• DOI: http://doi.org/10.5124/jkma.2010.53.4.270

Abstract

In this article, I will survey the major genetic susceptibility and somatic genetic alterations involved in gastric cancer and adenoma. These include germline and somatic genetic alterations in oncogenes, tumor suppressor genes, and apoptosis-related genes. A small proportion of gastric cancers arise as a consequence of hereditary predisposition caused by specific germline mutations in E-cadherin, mismatch repair genes, adenomatous polyposis coli, and STK11. Aberrant expression of activation induced cytidine deaminase, triggered by Helicobacter pylori infection, accumulates with genetic mutations of oncogenes and tumor suppressor genes, including p53 and CTNNB1. Inactivation of trefoil factor family 1, which is a gastric specific tumor suppressor, occurs in gastric adenomas and cancers. Ectopic expression of CDX2 leads to intestinal metaplasia and defective Cdx2 expression accelerates the transformation of metaplastic cells to gastric cancer. Genetic alterations of p53 and genes related to Wnt signaling pathway and microsatellite instability occur early in the development of gastric carcinoma, indicating that detection of certain genetic alterations in adenomas may be indicative of malignant transformation. In addition, inactivation of apoptosis-inducing gene caused by mutations may be an escaping mechanism against apoptotic cell death and contribute to the progression of gastric cancer. Although the results of many studies are contradictory with one another, genetic alterations in oncogenes and tumor suppressor genes are present even in gastric adenoma and increase in frequency during multistep gastric carcinogenesis. Genetic alterations described herein, and from as yet unidentified target genes in gastric cancer cells, will guide us towards more effective risk assessment, diagnosis, and treatment.

Keyword

Gastric cancer; Mutation; Oncogene; Tumor suppressor gene; Apoptosis

MeSH Terms

Adenoma
Apoptosis
Cadherins
Cell Death
Cytidine Deaminase
DNA Mismatch Repair
Genes, APC
Genes, Tumor Suppressor
Genetic Predisposition to Disease
Germ-Line Mutation
Helicobacter pylori
Humans
Lotus
Metaplasia
Microsatellite Instability
Oncogenes
Peptides
Risk Assessment
Stomach Neoplasms
United Nations
Wnt Signaling Pathway
Cadherins
Cytidine Deaminase
Peptides

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