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Molecular Pathology Of Oral Cancer: Clinical Implications | 68025
Our Group organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.
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-β), rs2071214 (Survivin),
rs13026208 (GALNT13), rs3803300 (AKT1), rs187115 (CD44), rs1982073 (TGFβ), rs1229984 (ADH1B), rs187238 (IL-18)
and rs189037 (ATM). Whereas 50% decreased risk was observed with alternate genotypes in PREX2 and TGFβ. 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.
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