title: Promoter hypermethylation and quantitative expression analysis of CDKN2A (p14ARF and p16INK4a) gene in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Abnormal hypermethylation of the CDKN2A (p14ARF and p16INK4a) gene can lead to repression of gene expression and contribute to carcinogenesis and tumor progression.
  
  
  METHODS
  In esophageal squamous cell carcinoma (ESCC), the promoter methylation of the p14ARF and p16INK4a gene was investigated in 38 cases by methylation-specific PCR and the expression of each gene in 18 cases was quantified by real-time quantitative reverse transcription-PCR.
  
  
  RESULTS
  Aberrant methylation of p14ARF and of p16INK4a was detected in 23 (61%) and 29 (76%) cases, respectively. No relationship was found between clinicopathological variables and p14ARF or p161NK4a promoter methylation. A statistically significant association between p14ARF methylation status and mRNA expression was found (p=0.0441). Regarding p14ARF, a low expression group showed a significantly higher proportion of cases with deep invasion of tumor, lymph node metastasis, and a high TNM stage of disease (p=0.0474, 0.0474, and 0.0441, respectively), and a significantly poor prognosis (p=0.0402). Regarding p161NK4a, no relationship was found among the methylation status, mRNA expression and clinicopathological variables, including survival.
  
  
  CONCLUSIONS
  Our results suggest that methylation is the predominant mechanism of inactivation of the p14ARF gene in ESCC. The decrease in p14ARF gene expression associated with invasive and metastatic phenotypes may be significant as an indicator of the malignant potential of human ESCC.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Japan. shuito@sc5.so-net.ne.jp
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ito
authors.forename: Takefumi
authors.initials: T
authors.lastname: Ohga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamada
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D025803:Tumor Suppressor Protein p14ARF / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF