Otolaryngology: Open Access
Open Access

Abstract

Oral cancer is a major health concern in India being the most common cancer in males and fifth most common cancer females and annual incidence of 77,003 new cancer cases, contributing 26% of the global oral cancer burden. Somatic mutations, aberrant expression, epigenomic regulation and genomic SNPs constitute specific alterations in oral cancer. The focus of our group investigating the molecular pathology of oral cancer is on identification of predictive biomarkers to indicate risk of oral cancer and molecular markers for early diagnosis, prognosis and as therapeutic targets. Somatic mutations in p53, H.ras, EGF-R and NOTCH1 have been observed in 30-60% patients and epigenetic deregulation via hypermethylation in p15/16, DAPK, MGMT, MLH1 and E-Cadherin in 36-50% patients; histone modification in H3 histone via methylation in 39- 47% and acetylation in 37-80% and miRNA deregulation in 70% oral cancer patients, providing excellent targets for specific treatment. Several single nucleotide polymorphisms (SNPs) as genomic variants in genes associated with cell cycle, proliferation, differentiation, metastasis, oxidative stress and apoptosis were examined using allelic discrimination real-time PCR assay or high resolution melt-curve analysis. Oral cancer patients demonstrated increased risk with OR 2 to 6.73 and narrow confidence intervals in SNPs including rs4512367 (PREX2), rs1800734 (MLH1), rs34329 (p27), rs16944 (IL1-�²), rs2071214 (Survivin), rs13026208 (GALNT13), rs3803300 (AKT1), rs187115 (CD44), rs1982073 (TGF�²), rs1229984 (ADH1B), rs187238 (IL-18) and rs189037 (ATM). Whereas 50% decreased risk was observed with alternate genotypes in PREX2 and TGF�². Further, the somatic mutations in H.ras gene at codons 12/13/61 was used as a prototype target for identification of small molecules from Maybridge Hit Finder Library, for selective inhibition of constitutive activation of H.ras and consequent proliferation of oral cancer cells. The identified molecules may be potential single or combinatorial therapeutic agents. Thus, molecular biomarkers of oral cancer indicate clinical applications for better management of oral cancer patients.

Biography

Email: dhananjaya.saranath@nmims.edu