title: Promoter hypermethylation of death-associated protein kinase and p16 genes in vulvar lichen sclerosus.
abstract: OBJECTIVE
  The purpose of this study was to discuss our investigation of the hypermethylation of promoter regions of tumor suppressor genes, such as death-associated protein kinase (DAPK) and p16, in vulvar lichen sclerosus (LS), in comparison with a control group.
  
  
  METHODS
  Promoter hypermethylation of DAPK and p16 was investigated using 24 vulvar biopsies of patients with LS who had received no previous treatment. The control group was composed of 15 patients with no vulvar disease. The DNA of subjects was treated with sodium bisulphate, and the genes under study were subjected to methylation-specific polymerase chain reaction. The resulting polymerase chain reaction products were amplified and analyzed using a 10% polyacrylamide gel.
  
  
  RESULTS
  The mean age of the patients with LS was 57 years (the majority were postmenopausal). In the control group, the mean age of the patients was 50 years (p = .151). Methylation of the promoter region of DAPK was found in 4 (17%) of the 23 patients analyzed, and p16 promoter region methylation was found in 8 patients (35%). Two cases of methylation of the DAPK gene were also found to be methylated for the p16 gene. In the control group, no methylation was found in the patients analyzed for the DAPK gene and methylation was found in 3 (21%) of the 14 patients analyzed for the p16 gene (p = .190 and p = .316, respectively).
  
  
  CONCLUSIONS
  Methylation of the DAPK and p16 genes, although not sufficient to dictate prognosis of the disease, should not be underestimated because it may form part of a process of genetic and epigenetic alterations that in the future could become relevant to malignant transformation.
authors.affiliation: Vulvar Pathology Unit, Institute of Gynecology, Carlos Chagas Filho Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. suaide@oi.com.br
authors.forename: Susana
authors.initials: S
authors.lastname: Aidé
authors.forename: Fernanda Ribeiro
authors.initials: FR
authors.lastname: Lattario
authors.forename: Gutemberg
authors.initials: G
authors.lastname: Almeida
authors.forename: Isabel Chulvis
authors.initials: IC
authors.lastname: do Val
authors.forename: Maria da Glória Costa
authors.initials: Mda G
authors.lastname: Carvalho
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011401:Promoter Regions, Genetic; D014844:Vulva / Q000473:pathology; D007724:Vulvar Lichen Sclerosus / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases