Aberrant gene promoter methylation of E-cadherin, p16 INK4a , p14 ARF , and MGMT in Epstein-Barr virus-associated oral squamous cell carcinomas

The etiology of oral carcinogenesis appears to be multifactorial. There is emerging evidence of the presence of Epstein-Barr virus (EBV) in epithelial oral squamous cell carcinoma (OSCC), but an association of EBV with oral carcinogenesis has not yet been established. Although epigenetic alterations, such as aberrant DNA methylation, are known to contribute to the pathogenesis of oral cancer, the relationship of such alterations with EBV infection is little known. This study aimed to investigate the association between EBV infection and promoter methylation patterns of tumor-associated genes in OSCC tissues. A total of 165 of formalin-fixed paraffin-embedded OSCC tissues were studied (68 of EBV positive and 97 of EBV negative). The promoter methylation patterns were investigated for four tumor-associated genes, E-cadherin, p16 , p14 , and MGMT, by using methylation-specific polymerase chain reaction (MSP). The frequencies of gene promoter hypermethylation in all cases were 47.3% for E-cadherin, 92.7% for p16 , 74.5% for p14 , and 35.8% for MGMT. Interestingly, most of the analyzed gene promoters were more frequently hypermethylated in EBV-positive than EBV-negative cases, in particular the E-cadherin (56/22) and MGMT (38/21) gene promoters (p