臨床および医療生化学

概要

Epigenetic Modifications of Nucleotide Excision Repair Genes in Oral Squamous Cell Carcinoma

Cynthia Cyriac, Rajni Sharma, Gursonika Binepal, Naresh Panda and Madhu Khullar

Genotoxic exposure to tobacco carcinogens resulting in DNA damage is an important mechanism of oral squamous cell carcinoma (OSCC) etiology. Nucleotide Excision Repair (NER) pathway removes bulky DNA adducts, generated from tobacco exposure thereby playing a major role in initiation of OSCC. In addition to mutations, epigenetic modifications have also been shown to target DNA repair genes thereby modulating oral tumor genesis. We therefore examined the role of epigenetic alterations modulating expression of three NER genes; XPC, XPB and XPD involved in removal of adducts caused by major classes of tobacco carcinogens and their contribution to OSCC Methylation status of NER genes was assessed using methylation specific PCR (MSP) in biopsies taken from 52 OSCC patients, their surrounding margins and 27 normal controls. The mRNA levels were determined using quantitative real time PCR (qRT-PCR) and Chromatin immuno precipitation (ChIP) analysis was performed to examine histone modifications in selected NER genes. We did not observe any significant difference in promoter methylation of NER genes between OSCC patients and controls. Increased XPB mRNA levels (p 0.04) and higher prevalence of H3 acetylation of XPB (p 0.04) gene were observed in OSCC patients as compared to controls. Our findings suggest the epigenetic modifications regulating the expression of XPB gene may be involved in OSCC etiology.