EB virus-associated gastric carcinoma. Molecular mechanisms of DNA hypermethylation and strategy for gastric cancer therapy.

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Methylation array analyses demonstrated that EBV-associated GC showed genome-wide hypermethylation at CpG sites of promoter regions. We succeeded in reproducing this genome-wide methylation by EBV infection of the gastric cancer cell line, MKN7, which serves as an important experimental system to investigate the molecular mechanisms. We demonstrated that a viral latent protein, LMP2A, partially contributed to the DNA hypermethylation. A possible virus-reactivating therapy was evaluated with inhibitors of DNA methylation and proteosome.