Promoter hypermethylation in Indian primary oral squamous cell carcinoma

Authors

  • Jatinder Kaur,

    1. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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  • Semra Demokan,

    1. Department of Otolaryngology-Head and Neck Surgery, John Hopkins Medical Institutions, Baltimore, MD
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  • Satyendra Chandra Tripathi,

    1. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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  • Muzafar Ahmad Macha,

    1. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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  • Shahnaz Begum,

    1. Department of Pathology, John Hopkins Medical Institutions, Baltimore, MD
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  • Joseph A. Califano,

    Corresponding author
    1. Department of Otolaryngology-Head and Neck Surgery, John Hopkins Medical Institutions, Baltimore, MD
    • Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, 601 North Caroline Street, 6th Floor, Baltimore, MD 21287-0910
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    • Tel: 410-502-5133, Fax: 1-410-614-1411

  • Ranju Ralhan

    Corresponding author
    1. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
    2. J & M Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, ON, Canada
    3. Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto, ON, Canada
    4. Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
    5. Department of Otolaryngology-Head and Neck Surgery, University of Toronto; Toronto, ON, Canada
    6. Department of Chemistry, York University, Toronto, ON, Canada
    7. Centre for Research in Mass Spectrometry, York University, Toronto, ON, Canada
    • Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, 600 University Avenue, Room 6-500, Toronto, Ontario, Canada M5G 1X5
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    • Tel: 1-416-586-4800 x 6426, Fax: 1-416-586-8628


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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