Promoter hypermethylation in Indian primary oral squamous cell carcinoma |
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| Authors: | Jatinder Kaur Semra Demokan Satyendra Chandra Tripathi Muzafar Ahmad Macha Shahnaz Begum Joseph A Califano Ranju Ralhan |
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| Institution: | 1. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India;2. Department of Otolaryngology‐Head and Neck Surgery, John Hopkins Medical Institutions, Baltimore, MD;3. Department of Pathology, John Hopkins Medical Institutions, Baltimore, MD;4. Tel: 410‐502‐5133, Fax: 1‐410‐614‐1411;5. J & M Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, ON, Canada;6. Department of Otolaryngology‐Head and Neck Surgery, Mount Sinai Hospital, Toronto, ON, Canada;7. Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada;8. Department of Otolaryngology‐Head and Neck Surgery, University of Toronto;9. Toronto, ON, Canada;10. Department of Chemistry, York University, Toronto, ON, Canada;11. Centre for Research in Mass Spectrometry, York University, Toronto, ON, Canada;12. Tel: 1‐416‐586‐4800 x 6426, Fax: 1‐416‐586‐8628 |
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| 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, p16INK4a 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 p16INK4a 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 p16INK4a 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 p16INK4a 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 p16INK4a 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. |
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| Keywords: | hypermethylation EDNRB KIF1A OSCC p16INK4a DCC nodal metastasis |
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