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American Head & Neck Society
July 21-25, 2012
Metro Toronto Convention Centre
Toronto, ON, Canada


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WHOLE GENOME CPG METHYLATION EVALUATION BY NON ISOTOPIC CYTOSINE EXTENSION ASSAY IN THE MULTISTEP CARCINOGENESIS MODEL OF ORAL SQUAMOUS CELL CARCINOMA

Presentation: P161
Topic: Basic Science
Type: Poster
Date: Sunday - Tuesday, July 22 - 24, 2012
Session: Designated Poster viewing times
Authors: Raghu A Radhakrishnan, PhD, Kapaettu Satyamoorthy, PhD
Institution(s): Manipal College of Dental Sciences, Manipal University, Manipal

Objective: The oral cancer epidemic which is increasingly more in developing countries is due to the combined effect of ageing of population and greater exposure to cancer risk factors, predisposing both genetic and epigenetic aberrations. DNA methylation as an epigenetic mark leads to modified gene expression and result in tumorigenesis by mutation in CpG hotspots, global hypomethylation and hypermethylation of CpG islands. Study design: Methylation profiling was carried out by cytosine extension assay for assessment of random methylation patterns in the experimental progression model of oral cancer which included normal oral mucosal tissues (n=10), leukoplakia (n = 10), erythroplakia/carcinoma in situ (n = 10) and oral squamous cell carcinoma (n = 10) using nanogram quantity of genomic DNA. Results: Cancer DNA showed a higher percentage of biotin incorporation following Hpa II digestion compared to its matched normal DNA (p < 0.001). Hpa II binding sites for biotinylated 14-dCTP increased with progression of disease process suggesting that DNA from oral cancer tissue was increasingly hypomethylated with respect to normal. Conclusion: The proposed model suggests that patients with oral cancer and those with potentially malignant oral disorders exhibit global hypomethylation compared to unaffected normal mucosa.

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