DNA methylation in choriocarcinoma

Epigenetika je znanstvena disciplina u biologiji koja proučava nasljedne promjene koje nisu uzrokovane promjenom u molekuli deoksiribonukleinske kiseline. Posebna je pažnja usmjerena na važnost epigenetskih mehanizama u regulaciji organizacije kromatina i ekspresiji gena, a čija promjena potaknuta od strane okoliša i vanjskih faktora može potaknuti razvoj tumora aktivacijom onkogena ili inaktivacijom gena supresora tumora. Najistraženija epigenetska modifikacija je metilacija DNA koja opisuje kovalentnu adiciju metilne skupine na citozinski prsten u citozin-gvanin dinukleotidnom kompleksu. Metilacija promotora gena dovodi do heterokromatizacije čime se smanjuje ekspresija gena. Koriokarcinom je zloćudni tumor epitela korionskih resica, često praćen sa stečenim genomskim abnormalnostima. Najčešće se širi hematogeno, a klinički se očituje oskudnim vaginalnim krvarenjem. Patološko-histološka metoda je zlatni standard u dijagnostici, a terapija se bazira na jednom ili kombinaciji više kemoterapeutika. Stanice koriokarcinoma pokazuju ukupno povišen stupanj metilacije u promotorskim regijama gena u usporedbi sa stanicama fiziološkog trofoblasta. Hipermetilirani su geni supresori tumora, uključujući gene regulatore staničnog ciklusa, gene zadužene za popravak i zaštitu DNA, apoptozu, staničnu adherenciju i proces metastaziranja. Intenzivno se istražuju lijekovi koji inhibiraju metilaciju DNA poznati kao demetilirajući agensi, od kojih je najpoznatiji decitabin.Epigenetics is the scientific discipline within the field of biology which studies heritable changes that are not caused by a change in a DNA molecule. Special attention is focused on the importance of epigenetic mechanisms in the regulation of chromatin organization and gene expression, and their changes by environmental and external factors can trigger tumor development by activation of oncogenes or inactivation of tumorsuppressors. The most explored epigenetic modification is DNA methylation. It represents a covalent addition of methyl groups to cytosine ring in cytosine-guanine dinucleotide complex. Gene promoter methylation leads to heterochromatization. Choriocarcinoma is a malignant tumor of epithelial chorionic villi which is often accompanied with acquired genomic abnormalities. It is characterized by early hematogenous spread and clinically manifests with poor vaginal bleeding. Histopathologic diagnosis is the gold standard and the therapy is based on the combination of one or more chemotherapeutic agents Choriocarcinoma cells show an increased total level of methylation in the gene promoter regions as compared with the physiological trophoblast cells. Tumorsuppressor genes are hypermethylated, including regulators of the cell cycle, the genes responsible for the repair and protection of DNA, apoptosis, cell adherence and the process of metastasis. Drugs that inhibit DNA methylation known as demethylating agents, most notably decitabine, are under extenisive research