Promoter hypermethylation of CDKN2A, MGMT, MLH1, and DAPK genes in laryngeal squamous cell carcinoma and their associations with clinical profiles of the patients

Head Neck. 2014 Aug;36(8):1103-8. doi: 10.1002/hed.23413. Epub 2013 Oct 7.


Background: Laryngeal squamous cell carcinoma (laryngeal SCC) is a frequently occurring cancer of the head and neck area. Epigenetic changes of tumor-related genes contribute to its genesis and progression.

Methods: We assessed promoter methylation status of the selected genes (CDKN2A, MGMT, MLH1, and DAPK) using methylation-sensitive high resolution melting (MS-HRM) in 100 patients with laryngeal SCC and studied the correlations with clinical characteristics.

Results: The prevalence of promoter methylation in MGMT, CDKN2A, MLH1, and DAPK was 59 of 97 (60.8%), 46 of 97 (47.4%), 45 of 97 (46.4%), and 41 of 97 patients (42.3%), respectively. Significantly increased methylation of CDKN2A was observed in heavy smokers. Epigenetic inactivation of CDKN2A and MLH1 were found to be associated with lymph node involvement. An inverse correlation was present between MLH1 methylation and alcohol consumption.

Conclusion: Our results strongly suggest that deregulation of p16-associated, and MLH1-associated pathways, because of promoter hypermethylation, is associated with increased cancer cell migration, tumor invasiveness, and, thus, aggressive phenotype.

Keywords: CDKN2A; MLH1; laryngeal carcinoma; lymph node metastases; promoter hypermethylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Bulgaria
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Death-Associated Protein Kinases / genetics*
  • Female
  • Humans
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Male
  • Middle Aged
  • MutL Protein Homolog 1
  • Nuclear Proteins / genetics*
  • Prevalence
  • Promoter Regions, Genetic
  • Tumor Suppressor Proteins / genetics*


  • Adaptor Proteins, Signal Transducing
  • Cyclin-Dependent Kinase Inhibitor p16
  • MLH1 protein, human
  • Nuclear Proteins
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • Death-Associated Protein Kinases
  • MutL Protein Homolog 1
  • DNA Repair Enzymes