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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
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Aberrant promoter hypermethylation of multiple genes in head and neck squamous cell carcinoma

Sajeev K Puri1, Lingbao Si, Chun-Yang Fan

  • 1Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. purisajeevk@uams.edu

American Journal of Otolaryngology
|January 7, 2005
PubMed
Abstract

Insights

Promoter hypermethylation of DNA repair and tumor-suppressor genes is common in head and neck cancer. Hypermethylation of multiple genes, including hMLH1, MGMT, and p16, significantly improves disease-free survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Epigenetic alterations, specifically promoter hypermethylation, are crucial in the development of head and neck squamous cell carcinoma (SCCHN).
  • This process can inactivate critical genes involved in tumor suppression and DNA repair.

Purpose of the Study:

  • To characterize the promoter methylation profiles of DNA repair genes (hMLH1, MGMT) and the tumor-suppressor gene (p16) in SCCHN.
  • To correlate these methylation profiles with clinical parameters and patient survival.

Main Methods:

  • DNA was extracted from 51 SCCHN tissue samples.
  • Methylation-specific PCR was employed to analyze promoter hypermethylation of hMLH1, MGMT, and p16 genes.

Main Results:

  • Aberrant promoter hypermethylation was detected in at least one gene in 62% of SCCHN cases.
  • Hypermethylation rates were 23% for hMLH1, 30% for MGMT, and 36% for p16.
  • Hypermethylation of two or more genes was significantly associated with improved 2-year disease-free survival (100% vs. 46%).

Conclusions:

  • Promoter hypermethylation of hMLH1, MGMT, and p16 is a frequent event in SCCHN.
  • The hypermethylation of multiple genes (2 or 3) is a significant predictor of improved disease-free survival.
  • A correlation was observed between alcohol use history and MGMT gene hypermethylation.

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