Summary:
Objective: To summarize the significance of methylation in HPV16 genome to cervix cancerogenesis.
Design: Review.
Setting: Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute,
Brno.
Subject and Method: Human papillomaviruses, especially HPV16, are the most frequent causative agents
of cervical intraepithelial neoplasia and cervical carcinoma. Their ability to initiate transformation of
infected epithelial cells fully depends up production of viral early phase proteins E6 and E7. Affected
keratinocytes activate defensive mechanisms based on inhibition of viral DNA transcription by changes
in chromatin structure like DNA methylation or histon deacetylation and therefore prevent
transcriptional factors from binding to target promoters and from the production of viral oncoproteins.
Conclusion: Research into epigenetic mechanisms of gene silencing clearly showed their important roles
in etiology of cancer. Recent findings confirm the significance of methylation of HPV16 oncogenes
leading to block of neoplastic transformation, and simultaneously they indicate new therapeutic
possibilities linked with reactivation of methylated tumor supressors.
Key words:
cervix carcinoma, HPV16, oncoproteins E6 and E7, methylation
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