Global and non‐random CpG‐island methylation in gastric carcinoma associated with Epstein‐Barr virus

DNA hypermethylation may play a primary role in the genesis of Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) (EBVaGC). Methylation-specific PCR targeting CpG-islands demonstrated markedly increased methylation of specific genes, such as p14, p15 and p16 genes, in EBVaGC in vivo. A high frequency of methylation was observed in an EBVaGC strain of severe combined immunodeficiency mice, and the expression of methylated genes in the strain was apparently lower than the expression of the unmethylated genes in EBV-negative GC strains. Although over-expression of DNA methyltransferases (DNMTs) is known to be associated with some human cancers, real-time PCR demonstrated that DNMTs expression was suppressed in EBVaGC. The DNA methylation of specific genes, independently of DNMTs expression, may be important in the development of EBVaGC.