DNA hypermethylation in gastric cancer

Aliment Pharmacol Ther. 2004 Jul;20 Suppl 1:131-42. doi: 10.1111/j.1365-2036.2004.01984.x.

Abstract

Background: Transcriptional silencing of tumour suppressor genes by DNA hypermethylation plays a crucial role in the progression of gastric cancer. Many genes involved in the regulation of cell cycle, tissue invasion, DNA repair and apoptosis have been shown to be inactivated by this type of epigenetic mechanism.

Results: Recent studies have demonstrated that DNA hypermethylation begins early in cancer progression, and in some cases, may precede the neoplastic process. Ageing is associated with DNA hypermethylation, and may provide a mechanistic link between ageing and cancer. Several reports have indicated that Epstein-Barr virus-related gastric cancer is associated with a high frequency of DNA hypermethylation, suggesting that viral oncogenesis might involve DNA hypermethylation with inactivation of tumour suppressor genes. Hypermethylation of hMLH1 with the resulting loss of its expression is known to cause microsatellite instability, which reflects genomic instability associated with defective DNA mismatch repair genes in the tumour.

Conclusions: In conclusion, recent studies demonstrate that DNA hypermethylation is a crucial mechanism of inactivation of tumour suppressor genes in gastric cancer. A better understanding of DNA hypermethylation will provide us with new opportunities in the diagnosis and therapy of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism
  • Cell Line, Tumor
  • Core Binding Factor Alpha 3 Subunit
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA Methylation*
  • DNA, Bacterial / metabolism
  • DNA-Binding Proteins / metabolism
  • Epstein-Barr Virus Infections / metabolism
  • GTPase-Activating Proteins
  • Helicobacter Infections / metabolism
  • Helicobacter pylori
  • Humans
  • Precancerous Conditions / metabolism
  • Stomach Neoplasms / metabolism*
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism
  • Tumor Suppressor Protein p14ARF / metabolism
  • Tumor Suppressor Proteins / metabolism

Substances

  • Cadherins
  • Core Binding Factor Alpha 3 Subunit
  • Cyclin-Dependent Kinase Inhibitor p16
  • DLC1 protein, human
  • DNA, Bacterial
  • DNA-Binding Proteins
  • GTPase-Activating Proteins
  • RASSF1 protein, human
  • Runx3 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Proteins