title: Promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A genes in cervical carcinoma.
abstract: OBJECTIVE
  Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of human cancer. This study explored the relationship between promoter methylation and inactivation of the DAPK1, FHIT, MGMT, and CDKN2A genes in cervical cancer.
  
  
  METHODS
  The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A was investigated by using a methylation-specific polymerase chain reaction in 53 specimens of cervical cancer (42 squamous cell carcinoma, 11 adenocarcinoma), 22 specimens of intraepithelial neoplasia tissues, and 24 control normal cervical tissue specimens. The correlation of promoter methylation with the clinicopathological features of cervical cancer was analyzed. The expressions of DAPK1, FHIT, MGMT, and CDKN2A were detected by measuring relative mRNA levels.
  
  
  RESULTS
  The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A in cervical cancer vs. intraepithelial neoplasia vs. normal cervical tissue was 75.5 vs. 31.8 vs. 4.2 % (p < 0.0001), 66.0 vs. 59.1 vs. 25.0 % (p = 0.0033), 34.0 vs. 27.3 vs. 20.8 % (p = 0.76), and 17.0 vs. 31.8 vs. 8.3 % (p = 0.11), respectively. The methylation of the promoter region significantly decreased the expression of only DAPK1 (p = 0.03). The methylation rate of the DAPK1 gene promoter was significantly higher in cervical cancer tissues than in cervical intraepithelial neoplasia and normal cervical tissues.
  
  
  CONCLUSIONS
  Promoter methylation may therefore lead to the inactivation of the DAPK1 gene, and may be related to the progression of cervical oncogenesis.
authors.affiliation: Division of Obstetrics and Gynecology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo Ward, Niigata, 951-8510, Japan, chiaki-b@med.niigata-u.ac.jp.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Banzai
authors.forename: Koji
authors.initials: K
authors.lastname: Nishino
authors.forename: Jinhua
authors.initials: J
authors.lastname: Quan
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yoshihara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sekine
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yahata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000096:biosynthesis / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000096:biosynthesis / Q000235:genetics*; D064550:Death-Associated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D064550:Death-Associated Protein Kinases; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C515491:MGMT protein, human; C579096:DAPK1 protein, human