title: 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(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% (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.
authors: Department of Pathology, Nara Medical University School of Medicine, Nara, Japan. eishida@naramed-u.ac.jp
authors: Eiwa
authors: E
authors: Ishida
authors: Mitsutoshi
authors: M
authors: Nakamura
authors: Keiji
authors: K
authors: Shimada
authors: Tomonori
authors: T
authors: Higuchi
authors: Keisuke
authors: K
authors: Takatsu
authors: Katsunari
authors: K
authors: Yane
authors: Noboru
authors: N
authors: Konishi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology*; D002648:Child; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics
chemical_list: D025803:Tumor Suppressor Protein p14ARF