DNA methylation as a marker for the past and future.

Aberrant methylation of CpG islands in promoter regions can permanently inactivate tumor-suppressor genes, as mutations and chromosomal abnormalities do. In gastric cancers, CDKN2A, CDH1, and MLH1 are inactivated more frequently by aberrant methylation than by mutations, and novel tumor-suppressor genes inactivated by promoter methylation are being identified. We recently found that Helicobacter pylori (HP), a potent gastric carcinogen, induces aberrant methylation in gastric mucosae. When a panel of CpG islands was examined, some CpG islands were consistently methylated in gastric mucosae of individuals with HP infection, while others were resistant. The amount of methylated DNA molecules in the gastric mucosae (methylation level) fluctuated while active HP infection was present, but decreased after it was no longer present. Among individuals without active HP infection, methylation levels in the gastric mucosae were higher in individuals with gastric cancers than in those without. DNA methylation is emerging as a promising marker for past exposure to carcinogens and future risk of cancers.