Promoter methylation and loss of p16(INK4a) gene expression in head and neck cancer

Head Neck. 2012 Oct;34(10):1470-5. doi: 10.1002/hed.21949. Epub 2011 Nov 22.

Abstract

Background: Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. In this study we aimed to evaluate aberrant p16(INK4a) gene promoter methylation in patients with head and neck cancer.

Methods: Methylation of the gene was investigated by bisulfite modification/methylation-specific polymerase chain reaction and gene expression levels were analyzed by quantitative reverse transcription-polymerase chain reaction in tumors and matched normal tissue samples from Turkish patients with head and neck cancer.

Results: The promoter region of the p16(INK4a) gene was methylated in 67.5% and 28.6% of the primary tumors and the corresponding normal tissue, respectively. This difference was highly significant. In concordance, p16(INK4a) gene expression was downregulated in 67.5% of the tumor samples. Methylation and the absence of expression in the tumors were observed in 48% of the patients.

Conclusions: Our data indicate that methylation of the p16(INK4a) gene is a frequent event in primary head and neck cancer and that it plays a major role in the silencing of p16(INK4a) gene expression during tumor development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Confidence Intervals
  • DNA Methylation / genetics
  • DNA, Neoplasm / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing*
  • Genes, p16*
  • Genetics
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Promoter Regions, Genetic*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sampling Studies
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • DNA, Neoplasm