title: Promoter hypermethylation in Indian primary oral squamous cell carcinoma.
abstract: We evaluated promoter hypermethylation of a panel of tumor suppressor genes as a means to detect epigenetic alterations in oral squamous cell carcinomas (OSCC) of Indian-origin and compare with North-American head and neck squamous cell carcinomas (HNSCC). Quantitative-methylation-specific PCR was used to investigate the promoter methylation status of DCC, EDNRB, p16(INK4a) and KIF1A in 92 OSCC, and compared to 48 paired normal tissues and 30 saliva and sera samples from healthy control subjects. Aberrant methylation of at-least one of these genes was detected in 74/92 (80.4%) OSCC; 72.8% at EDNRB, 71.7% at KIF1A, 47.8% at p16(INK4a) and 58.7% at DCC; and in 5 of 48 (10.4%) normal oral tissues. None of the saliva and sera samples from controls exhibited DNA methylation in these four target genes. Thirty-two of 72 node positive cases harbored p16(INK4a) and DCC hypermethylation (p = 0.005). Thus, promoter hypermethylation in genes analyzed herein is a common event in Indian OSCC and may represent promising markers for the molecular staging of OSCC patients. We found higher frequency of p16(INK4a) methylation (47.8%) in this Indian cohort in comparison with a North-American cohort (37.5%). In conclusion, aberrant methylation of EDNRB, KIF1A, DCC and p16(INK4a) genes is a common event in Indian OSCC, suggesting that epigenetic alterations of these genes warrant validation in larger studies for their potential use as biomarkers.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Jatinder
authors.initials: J
authors.lastname: Kaur
authors.forename: Semra
authors.initials: S
authors.lastname: Demokan
authors.forename: Satyendra Chandra
authors.initials: SC
authors.lastname: Tripathi
authors.forename: Muzafar Ahmad
authors.initials: MA
authors.lastname: Macha
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Begum
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.forename: Ranju
authors.initials: R
authors.lastname: Ralhan
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D007194:India; D016547:Kinesins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D044023:Receptor, Endothelin B / Q000235:genetics
chemical_list: C094065:KIF1A protein, human; D044023:Receptor, Endothelin B; D016547:Kinesins
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