20.500.12556/DiRROS-17984 The relationship between DNA methylation and expression of three different DNA methyltransferases in ovarian cancer Odnos med stopnjo metilacije DNA in izražanjem treh različnih DNA metiltransferaz pri ovarijskem karcinomu Background. DNA methylation in mammals is required for embryonic development, X chromosome inactivation and imprinting. Previous studies have shown that methylation patterns become abnormal in malignant cells and may contribute to tumorigenesis. The aim of the study was to ascertain the relationship between overall DNA methylation and the expression of DNMT1, DNMT3A and DNMT3B in ovarian cancer samples. Material and methods. DNA digestion with either methylation sensitive HpaII, or methylation insensitive MspI restriction endonuclease and quantitative reverse transcription-PCR methods were used to analyse global methylation levels and expression levels of five ovarian cancerand three normal ovarian tissue samples. Results. All five analysed cancer samples were hypomethylated. The differences of methylation levels between normal ovarian tissue and carcinoma samples were statistically significant (P<0.05). All five cancer samples showed overexpression of DNMT3A and DNMT3B, and only two ovarian tumour samples showed overexpression of DNMT1. There was no correlation between global demethylation and expression levels for the three different DNMTs.Conclusion. Genome wide hypomethylation facilitates tumor development with predisposition of cells to structural and numerical chromosomal aberrations but the paradox of the global hypomethylation observed in cancer cells and the high levels of DNMTs that arepresent in these cells still remain to be resolved. Izhodišča. Metilacija DNA igra pomembno vlogo v razvoju zarodka, pri inaktivaciji kromosoma X ter pri izražanju "imprinting" genov. Raziskave so pokazale, da imajo maligne celice spremenjen vzorec metilacije DNA, spremembe DNA metilacije pa sodelujejo v procesu kancerogeneze. Namen dela je bil ugotoviti ali obstaja povezava med stopnjo metilacije DNA ter izražanjem treh DNA metil-transferaz (DNMT) in sicer DNMT1, DNMT3A in DNMT3B v vzorcih ovarijskih karcinomov. Materiali in metode. Za določitev stopnje metilacije DNA v petih vzorcih ovarijskega karcinoma in treh vzorcih morfološko normalnihjajčnikov je bila DNA izpostavljena delovanju bodisi za metilacijo občutljive HpaII, ali za metilacijo neobčutljive MspI restrikcijske endonukleaze. Za določitev stopnje izražanja treh DNMT v vzorcih smo uporabilimetodo kvantitativnega PCR. Rezultati. DNA vseh petih ovarijskih karcinomov je bila globalno hipometilirana. Razlike med stopnjo metilacije DNAmed ovarijskimi karcinomi in normalnim tkivom jajčnika so bile statistično značilne (p<0.05). Vseh pet ovarijskih karcinomov je kazalo prekomerno izražanje DNMT3A in DNMT3B, medtem ko smo našli prekomerno izražanje DNMT1 samo v dveh vzorcih. Med stopnjo globalne demetilacije in izražanjem treh različnih DNMT ni bilo statistično značilnik korelacij. Zaključki. Hipometilacija genoma igra pomembno vlogo pri nastanku tumorjev saj vodi v strukturne in numerične kromosomske nepravilnosti v tumorskih celicah, vendar pa ostaja paradoks med stopnjo globalne hipometilacije na eni strani in povečanim izražanjem DNMT na drugi še vedno nerazjasnjen. true false true Slovenian Medical Association - Slovenian Association of Radiology, Nuclear Medicine Society, Slovenian Society far Radiotherapy and Oncology, and Slovenian Cancer Society Ljubljana Angleški jezik Slovenski jezik by Authors Neznano 2024-01-25 09:50:59 2024-01-25 09:50:59 2024-01-26 03:50:48 0000-00-00 00:00:00 2000 0 0 BSDOCID56905; str. 369-374 št. 4 Letn. 34 2000 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2000-01-01 616-006 1318-2099 12586969 RAZ_Cor_Andrej_2000.pdf RAZ_Cor_Andrej_2000.pdf 1 25B876682916207420610D8132133782 11ceb6331ed5c73159cbd9a92b7912b35591a4984626507f3cec3bf7ddc1ce27 06e8067c-bb5f-11ee-b0d4-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=24394 Onkološki inštitut Ljubljana 0 0 0