Promoter hypermethylation patterns of death-associated protein kinase and p16 genes in vulvar lichen sclerosus.
OBJECTIVE
This article aimed to investigate the hypermethylation of promoter regions of tumor suppressor genes, such as death-associated protein kinase (DAPK) and p16, in vulvar lichen sclerosus (LS).


METHODS
The promoter hypermethylation of DAPK and p16 was investigated from 15 vulvar biopsies of patients with LS who had had no previous treatment. DNA was treated with sodium bisulfate and underwent methylation-specific polymerase chain reaction of these genes. The amplified polymerase chain reaction products were analyzed by 10% polyacrylamide gel.


RESULTS
The mean age of the patients was 57 years (most were postmenopausal). Methylation of the promoter region of DAPK was found in 2 (13%) of 15 patients analyzed, and p16 promoter region methylation was found in 7 patients (47%). The samples that showed DAPK methylation also showed p16 methylation.


CONCLUSIONS
Methylation of DAPK and p16 represent alterations that might occur in cell cycle control in LS. The hypothesis is that patients who had methylated genes in this study, mainly the 2 cases in which there has been methylation in both studied genes, may be more susceptible to the development of differentiated vulvar intraepithelial neoplasia or vulvar cancer. Methylation may play a role in progress of vulvar carcinogenesis.
Aidé
Susana
S
Vulvar Pathology Unit, Institute of Gynecology, Carlos Chagas Filho Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. suaide@oi.com.br
Lattario
Fernanda Ribeiro
FR
Almeida
Gutemberg
G
do Val
Isabel Chulvis
IC
Carvalho
Maria da Glória Costa
Mda G
D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D057089:Pathology, Molecular / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D007724:Vulvar Lichen Sclerosus / Q000473:pathology*
D051017:Apoptosis Regulatory Proteins; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D004247:DNA; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases