Evaluation of DAPK gene methylation and HPV and EBV infection in cervical cells from patients with normal cytology and colposcopy.
OBJECTIVE
Evaluation of promoter methylation of the death-associated protein kinase (DAPK) gene and HPV and EBV infections in cervical cells from patients with normal cytology and colposcopy.


METHODS
Twenty women, who had been patients at the Institute of Gynecology of the Federal University of Rio de Janeiro (UFRJ) for routine examinations and who showed normal cytology and colposcopy, were selected for this work. Cervical brushings were used for DNA extraction, and the analysis of methylation patterns of the DAPK gene was done through chemical modification with sodium bisulfite. Analysis of viral infection was done using polymerase chain reaction (PCR).


RESULTS
Of the 20 patients studied, six (30%) presented methylation of the DAPK gene, five (25%) presented infection with EBV and three (15%) presented coinfection with HPV/EBV. Associating methylation with viral infection, we found methylated DAPK in one patient (16%) with EBV, in two patients (33%) with co-infection and in three patients (50%) with no viral infection.


CONCLUSIONS
In the present study, we verified, for the first time, the methylation pattern of the DAPK gene in cervical smears from patients with normal cytology and colposcopy. The results also showed the presence of viral infections in these patients. EBV infection, irrespective of whether associated with HPV or not, may contribute to cervical carcinogenesis as a cofactor. Methylation of the DAPK gene is associated with cell transformation, suggesting that DAPK methylation might be an important marker for the development of cervical epithelial neoplasias.
Lattario
Fernanda
F
Genetic Expression Control Laboratory, Carlos Chagas Filho Institute of Biophysics, UFRJ, Centro de Ciências da Saúde (CCS), Rio de Janeiro, Brazil. fernandalattario@gmail.com
Furtado
Yara Lucia
YL
Silveira
Filomena Aste
FA
do Val
Isabel Cristina
IC
Almeida
Gutemberg
G
da Costa Carvalho
Maria da Gloria
Mda G
D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology*; D003127:Colposcopy; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases