Promoter hypermethylation in Indian primary oral squamous cell carcinoma

Kaur J., Demokan S., Trıpathı S. C., Macha M. A., Begum S., Califano J. A., ...Daha Fazla

INTERNATIONAL JOURNAL OF CANCER, cilt.127, sa.10, ss.2367-2373, 2010 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 127 Sayı: 10
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1002/ijc.25377
  • Dergi Adı: INTERNATIONAL JOURNAL OF CANCER
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED)
  • Sayfa Sayıları: ss.2367-2373
  • Anahtar Kelimeler: hypermethylation, EDNRB, KIF1A, OSCC, p16(INK4a), DCC, nodal metastasis, ABERRANT METHYLATION, GENETIC ALTERATIONS, COLORECTAL-CANCER, LUNG-CANCER, EDNRB GENE, HEAD, P16, P16(INK4A), P14(ARF), DISEASE
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.