Promoter Region Hypermethylation and mRNA Expression ofMGMTandp16Genes in Tissue and Blood Samples of Human Premalignant Oral Lesions and Oral Squamous Cell Carcinoma

Abstract

Promoter methylation and relative gene expression of O6-methyguanine-DNA-methyltransferase (MGMT) andp16genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC). Methylation-specific PCR and reverse transcriptase PCR were performed in 146 tissue and blood samples from controls and patients with PMOLs and OSCC. In PMOL group, significant promoter methylation ofMGMTandp16genes was observed in 59% (P=0.0010) and 57% (P=0.0016) of tissue samples, respectively, and 39% (P=0.0135) and 33% (P=0.0074) of blood samples, respectively. Promoter methylation of both genes was more frequent in patients with OSCC, that is, 76% (P=0.0001) and 82% (P=0.0001) in tissue and 57% (P=0.0002) and 70% (P=0.0001) in blood, respectively. Significant downregulation ofMGMTandp16mRNA expression was observed in both tissue and blood samples from patients with PMOLs and OSCC. Hypermethylation-induced transcriptional silencing ofMGMTandp16genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy. Results support use of blood as potential surrogate to tissue samples for screening or diagnosing PMOLs and early OSCC.