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

• Published in: Head & neck Vol. 36; no. 8; pp. 1103 - 1108
• Main Authors: Pierini, Stefano, Jordanov, Stanislav H., Mitkova, Atanaska V., Chalakov, Ivan J., Melnicharov, Mincho B., Kunev, Kuncho V., Mitev, Vanio I., Kaneva, Radka P., Goranova, Teodora E.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.08.2014; Wiley Subscription Services, Inc
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adult; Aged; Bulgaria; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; CDKN2A; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Death-Associated Protein Kinases - genetics; DNA Methylation; DNA Modification Methylases - genetics; DNA Repair Enzymes - genetics; Female; Humans; laryngeal carcinoma; Laryngeal Neoplasms - genetics; Laryngeal Neoplasms - pathology; lymph node metastases; Male; Middle Aged; MLH1; MutL Protein Homolog 1; Nuclear Proteins - genetics; Prevalence; promoter hypermethylation; Promoter Regions, Genetic; Tumor Suppressor Proteins - genetics; lymph node metastases; MLH1; CDKN2A; laryngeal carcinoma; promoter hypermethylation
• ISSN: 1043-3074; 1097-0347
• DOI: 10.1002/hed.23413

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. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1103–1108, 2014