OP007: Aberrant methylation of genes in oral squamous cell carcinoma

Abstract

Backgound Carcinogenesis is a multistep process, characterized by the accumulation of genetic abnormalities and epigenetic aberrations without any alterations in the DNA sequence. Methylation profiling of tumour tissues has identified the epigenetic aberrations, especially silencing of promoter methylation has been reported as an early event in carcinogenesis. Methods Forty oral squamous cell carcinoma (OSCC) samples selected for methylation-specific polymerase chain (MSPCR) reaction and immunohistochemical staining (IHC). Chi Square and Fisher’s Exact tests were applied to determine the correlation between patient’s demographic and clinicopathological data with p16, DDAH2 and DUSP1 genes using SPSS version 17.0. A p value Results In MSPCR, an overall analysis of tumours was made, where 100% (40/40) of the tumours revealed the hypermethylation of the promoter region was present in at least one of the genes analyzed. In 42.5% (17/40) of the tumours, the promoter hypermethylation was present in two of the genes analyzed and in 55% (22/40) hypermethylation was present in all of the three genes studied. Frequencies of methylation status of promoter hypermentylation of p16, DDAH2 and DUSP1 showed 78%, 80% and 88% positivity, respectively in our study. In IHC staining, DUSP1 revealed 42% of immunoreactivity. There was no statistically significant association between the presence of hypermethylation in the promoter regions of p16, DDAH2 and DUSP1 with the demographic data. However, a statistically significant association was found between p16 gene promoter region with tumour site of buccal, gum, tongue, and lip (p = 0.000). Conclusions Our findings reveal that the p16, DDAH2 and DUSP1 genes are aberrantly methylated in OSCC, which may serve as a diagnostic biomarker for OSCC patients’ prognosis in the future. In addition, aberrant methylation of DUSP1 genes more likely contribute to the loss of the protein expressions.