MEDIX, God. 19 Br. 104/105  •  Pregledni članak  •  Molekularna medicina HR ENG

Rak vrata maternice i metiliranje DNKCervical cancer and DNA methylation

Nina Milutin Gašperov, Magdalena Grce

Rak vrata maternice razvija se dulji niz godina kroz nekoliko stadija cervikalnih intraepitelnih neoplazija do invazivnog karcinoma. Progresija prekanceroznih lezija vrata maternice ovisi uglavnom o prisutnosti trajne infekcije s onkogenim tipovima humanog papiloma virusa (HPV). Osim toga, u progresiji do karcinoma značajnu ulogu imaju epigenetički događaji. Epigenetička promjena, kao metiliranje DNK promotorske regije gena, gdje započinje transkripcija, rezultira utišavanjem mnogih gena. Stoga transkripcijsko utišavanje putem metiliranja DNK ključnih gena koji kontroliraju diobu stanica te tumor-supresorskih gena, ima značajnu ulogu u nastanku raka. Ovaj epigenetički poremećaj prisutan u mnogim karcinomima može biti izliječen nakon tretiranja inhibitorima metiliranja DNK. U raku vrata maternice promijenjeno metiliranje je opisano u više od dvjesto gena, uključujući i tumorsupresorske gene, što znači da bi promjena metiliranja nekih gena mogla biti dobar biljeg promjena vrata maternice. Međutim, za sada promjena metiliranja niti jednog od opisanih gena u potpunosti ne udovoljava kriterijima dovoljne osjetljivosti i specifičnosti za populacijski probir. 

Ključne riječi:
cervikalna intraepitelna neoplazija; epigenetika; humani papiloma virus; neoplazme vrata maternice

Članak u cijelosti pročitajte u tiskanom izdanju MEDIX, God. 19 Br. 104/105

Cervical cancer develops gradually over many years through several stages ranging from cervical intraepithelial neoplasia to invasive cancer. The progression of cervical precancerous lesions essentially depends on the presence of persistent infection with oncogenic types of human papillomavirus. In addition, epigenetic events play a significant role in the development and progression of cancer in general. Epigenetic changes, such as DNA methylation in the promoter region of genes where transcription is initiated, results in inactivation and silencing of many genes. Transcriptional silencing through DNA methylation of critical growth regulators and tumour suppressor genes plays a major role in cancer. This deregulated epigenetic event in cancer can be reversed by DNA methylation inhibitors. In cervical cancer, altered DNA methylation is described for more than 200 genes, including tumour suppressor genes, representing potential biomarkers of cervical lesions. However, for now, change in methylation of any of the described gene does not fully meet the criteria of sufficient sensitivity and specificity for population screening. 

Key words:
cervical intraepithelial neoplasm; epigenetics; human papillomavirus; uterine cervical neoplasms