Hypermethylation of tumor suppressor and tumor-related genes in neoplastic and non-neoplastic gastric epithelia.

A number of tumor suppressor and tumor-related genes exhibit promoter hypermethylation with resultant gene silencing in human cancers. The frequencies of methylation differ among genes and genomic regions within CpG islands in different tissue types. Hypermethylation initially occurs at the edge of CpG islands and spreads to the transcription start site before ultimately shutting down gene expression. When the degree of methylation was quantitatively evaluated in neoplastic and non-neoplastic gastric epithelia using DNA microarray analysis, high-level methylation around the transcription start site appeared to be a tumor-specific phenomenon, although multiple tumor suppressor genes became increasingly methylated with patient age in non-neoplastic gastric epithelia. Quantitative analysis of DNA methylation is a promising method for both cancer diagnosis and risk assessment.