Frequent hypermethylation of DAPK, RARbeta, MGMT, RASSF1A and FHIT in laryngeal squamous cell carcinomas and adjacent normal mucosa.

Laryngeal cancers are the most frequent cancers of the head and neck region. While recent observations indicate the occurrence of an epigenetic field defect in head and neck cancer patients, a detailed exploration of the characteristic changes in the DNA methylation profile in laryngeal cancer patients was lacking. The aim of this study was to assess the methylation frequency of seven genes in a group of patients with primary laryngeal squamous cell carcinoma. Along tumor sections, matching samples of normal mucosa from epiglottis and trachea were analyzed. Gene methylation was assessed using the methylation-specific polymerase chain reaction. We found frequent gene hypermethylation in both the tumor and normal mucosa samples. The methylation of MGMT in tumor cells was associated with lymph node involvement. We report that laryngeal squamous cell carcinomas are characterized by frequent hypermethylation of DAPK, RARbeta, MGMT, RASSF1A and FHIT. Moreover, evidence is shown for the occurrence of a large epigenetically changed field of epithelial cells in laryngeal cancer patients. Our findings indicate the high prevalence of epigenetic abnormalities in laryngeal tumors.