DNA hypermethylation status of multiple genes in papillary thyroid carcinomas

Objective: The aim of this study was hypermethylation of multiple genes for papillary thyroid carcinomas ( PTCs). Methods: We examined 39 lesions using methylation- specific PCR to assess hypermethylation in genes, including p16(INK4a), p14(ARF), RB1, p27(Kip1) and 0(6)-MGMT. Homozygous deletions of p16(INK4a) and p14(ARF) were investigated by differential PCR, all with reference to clinicopathological factors. Results: We found methylation of p16(INK4a) in 35.9% (14/39); p14(ARF) in 2.6% (1/39); RB1 in 23.1% (9/39); p27(Kip1) in 15.4% (6/39), and 0(6)-MGMT in 15.4% (6/39). Hypermethylation of at least one of these genes was apparent in 66.7% (26/39). Homozygous deletions of p14(ARF) and p16(INK4a) were detected in 7.7 (3/39) and 2.6% (/39), respectively. In cases with p16(INK4a) alterations, tumors were significantly increased. A history of chronic thyroid disease and lymphocytic infiltration was significantly associated with p14(ARF) alterations, without regional lymph node metastases. Conclusions: Our data suggest that alterations in p16(INK4a), mainly hypermethylation, may be linked to tumor growth but not tumor development, while alterations in p14(ARF) may contribute to the induction of chronic inflammation-related PTCs. Copyright (c) 2007 S. Karger AG, Basel.