DNA Hypermethylation Status of Multiple Genes in Papillary Thyroid Carcinomas

Abstract

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^Kip1and 0⁶ -MGMT. Homozygous deletions of p16^INK4a and p14^ARF were investigated by differential PCR, all with reference to clinicopathological factors. Results: We foundmethylation 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 0⁶ -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% (1/39), 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.