Epigenetic silencing of WNT5A in Epstein-Barr virus-associated gastric carcinoma

Epstein-Barr virus (EBV) is responsible for the development of multiple tumors, including EBV-associated gastric carcinoma (EBVaGC), but little is known about its mechanisms in EBVaGC. WNT5A expression and promoter methylation were measured in 5 EBV-positive and 15 EBV-negative GC cell lines. The methylation status of 23 EBV-positive and 25 EBV-negative paired tumor/normal tissue samples was also examined. EBV-positive GC had no or very low expression of WNT5A but a high level of methylation in the promoter region. In contrast, EBV-negative GC had higher WNT5A expression and a lower level of promoter methylation. The reduced WNT5A expression could be restored by treatment with Aza, a methyltransferase inhibitor. Increased expression of WNT5Ain vitro inhibited β-catentin expression in EBVaGC cells (SNU719). These results suggest that hypermethylation of WNT5A induced by EBV may contribute to the development of EBVaGC. Ectopic introduction of WNT5A may have preventive/therapeutic potential for tumors with silenced WNT5A.