Promoter Hypermethylation Profile of Tumour Suppressor Genes in Oral Leukoplakia and Oral Squamous Cell Carcinoma

Abstract

Purpose of the Study: The present study was conducted to evaluate epigenetic alteration of five tumour suppressor genes in the oral precancer and cancer patients. Materials and Methods:The study was carried out in three groups namely control group of five people (normal healthy individuals), 10 oral leukoplakia patients and 10 oral squamous cell carcinoma patients. Incisional biopsy was done and part of the tissue sent for histological examination and part of tissue sent for hypermethylation study of p16, p15, hMLH, MGMT, E-cadherin tumour suppressor genes. Methylation specific polymerase chain reaction was carried out for detecting methylation in promoter regions of tumour suppressor genes. The resultant PCR products were run in a 2.5% agarose gel and the promoter hypermethylation status of the five tumour suppressor genes were analysed. Results:In oral Leukoplakia patients, 60% of methylation in the case of p16 gene, 30% of methylation in the case of MGMT gene and 60% of methylation in the case of E-cadherin gene. In oral Squamous cell carcinoma patients, 60% of methylation in the case of p16 gene, 40% of methylation in the case of MGMT, 60% of methylation in the case of E-cadherin gene, 20% in case of p15,10% in case of hMLH gene. Conclusion:Our results suggest that epigenetic mechanisms of inactivation of tumour suppressor genes, such as aberrant methylation of p16 and E-cadherin genes occur early in head and neck tumourigenesis and might play a role in the progression of these lesions.

DNA methylation markers for oral pre-cancer progression: A critical review

“…Interestingly, hyper-methylation of p16 has also been found to be a promising prognostic bio-marker for recurrence-free survival of oral and oro-pharyngeal cancers [19] . Other loci such as E-cadherin (adhesion molecule), mi-RNA genes and various other DNA repair genes which have been studied in oral cancers [7] are also being evaluated in oral pre-cancer [34] , [35] , [36] .…”

Evaluation of the two polymorphisms rs1801133 in MTHFR and rs10811661 in CDKN2A/B in breast cancer

“…24 CDKN2A/B mutations were associated with elevated risk of diseases, such as coronary artery disease 25,26 and melanoma 27 ; and were frequent in the wide spectrum of human cancers. [28][29][30][31][32][33][34][35][36][37][38] In the current study we aimed to evaluate the simultaneous association of both SNP rs1801133 in MTHFR and rs10881661 in CDKN2A/B genes with the risk of breast cancer.…”

WNT Signaling in Oral Cancer Initiating Cells

“…Epigenetic events are acquired and cause changes at the level of the phenotype by altering the structure of the chromatin, without affecting the genotype, seen as DNA hypermethylation and post-translational histone modifications (34). Promoter hypermethylation of tumor suppressor genes such as those encoding p16, MGMT and Ecadherin were commonly noted (up to 60%) in oral leukoplakias and OSCC (35). Also, hypermethylation of CDH1 and DAPK has been noted in OSCC (36)(37)(38).…”

“…Immunofluorescence studies for β-catenin and LEF-1 in normal epithelium………………………………………………………………………………. 35. …”