[Genetic and epigenetic factors of cervical tumor progression].
Infection with high risk papilloma viruses (HPV types 16, 18, and relative ones) initiates the development and progression of uterine neck cancer. The viral genome is found in pre-tumorous lesions (stage I to III intraepithelial neoplasias--CIN) and carcinomas, persisting in cells in episomal or integrated state. In all tumors, there is the expression of two viral transforming genes, E6 and E7, the main function of which is the inactivation of genes that suppress tumoral growth, p53 and retinoblastoma gene. In CIN and carcinomas, losses of heterozygosity are found in various chromosomes, mainly in the areas of suppressor genes; some of them can be specific for certain stages of the malignant process. Among epigenetic alterations, the main significance for the progress of the disease belongs to the methylation of the promoter areas of the genes involved in the process of cell division, which may be specific for each separate tumor and appears in approximately 30 to 40% of tumors. Another important epigenetic alteration is the increase in the expression of p16ink4a gene, which is the inhibitor of cyclin-dependent kinases; this appears at CIN I stage and may serve as an additional early diagnostic marker. Telomerase activity has been identified in all uterine neck tumors, but each tumor has its own spectrum of spliced RNA coding this enzyme. Expression microchip technique has shown that each tumor is individual according to the spectrum of "working" genes, and this spectrum varies in the process of tumor progression.
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D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D014626:Vaginal Smears
D017931:DNA Primers; D004279:DNA, Viral