@article{
author = "Petrović, Bojana and Perović, Milica and Novaković, Ivana and Atanacković, Jasmina and Popović, Branka and Luković, Ljiljana and Petković, Spasoje",
year = "2006",
abstract = "Background/aim: Among the genes involved in ovarian carcinogenesis, there has been increased interest in tumor-suppressor genes p53 and BRCA1. Both of the genes make control of cell cycle, DNA repair and apoptosis. The p53 is a "genome guardian" inactivated in more than 50% of human cancers, while BRCA1 mutations are found mostly in breast and ovarian cancer. The aim of this investigation was to establish the frequency of loss of heterozygosity (LOH) in the regions of the genes p53 and BRCA1 in ovarian carcinomas, and to analyze the association of LOH with the disease stage and prognosis. Methods. We analyzed 20 patients with a confirmed diagnosis of epithelilal ovarian carcinoma. DNA for molecular-genetic analysis was extracted from the tumor tissue and blood as normal tissue of each person. Microsatellite markers of the regions of genes p53 and BRCA1 were amplified by PCR method. The determination of allelic status of microsatellites and detection of LOH was performed after PAA gel electroforesis. Results. Both of the analyzed microsatellite markers were informative in 13/20 (65%) cases. In the region of gene p53, LOH was established in 4/13 (30.7%) tumors. One of them had histological gradus G1, one had gradus G2, and two of them had gradus G3, while all were with the International Federation of Gynecology and Obstetrics (FIGO) IIIc stage. In the region of gene BRCA1, LOH was detected in 5/13 (38.5%) tumors. Four of them had histological gradus G2, and one had gradus G3, while by the (FIGO) classification one was with stage Ib, one was with stage IIIb, while the three were with stage IIIc. LOH in both of the analyzed regions was detected in one tumor (7.7%), with histological gradus G3 and the FIGO IIIc stage. Conclusion. The frequency of LOH in epthelial ovarian carcinomas was 30.7% and 38.5% for p53 and BRCA1 gene regions, respectively. Most of tumors with LOH had histological gradus G2 or G3, and the clinical FIGO stage IIIc, suggesting the association of this occurrence with a later phase of the disease., Uvod/cilj: Među genima uključenim u proces ovarijumske karcinogeneze pažnju privlače tumor-supresor geni p53 i BRCA1. Oba gena kontrolišu ćelijski ciklus, reparaciju DNK i apoptozu. Dok je p53 univerzalni "čuvar genoma" čija se inaktivacija nalazi u više od 50% maligniteta čoveka, mutacije BRCA1 se nalaze pre svega kod karcinoma dojke i ovrijuma. Istraživanje je sprovedeno sa ciljem da se utvrdi učestalost gubitka heterozigotnosti (LOH) u regionima gena p53 i BRCA1 kod karcinoma ovarijuma i da se ispita njegova korelacija sa stadijumom i prognozom bolesti. Metode. Ispitivanjem je obuhvaćeno 20 bolesnica sa potvrđenom dijagnozom karcinoma ovarijuma. Za molekularno genetičku analizu DNK izolovana je iz tumorskog tkiva i krvi kao kontrolnog zdravog tkiva iste osobe. Mikrosatelitni markeri u regionu gena p53 i BRCA1 umnožavani su PCR metodom, a analiza alelskog statusa i pojave LOH je vršena nakon poliakril-amidinom (PAA) gel elektroforeze. Rezultati. Oba analizirana mikrosatelitna markera bila su informativna u po 13 do 20 slučajeva (65%). U regionu gena p53 nađen je LOH u 4 od 13 slučajeva (30,7%). Po jedan od ovih tumora bio je histološkog gradusa G1 i G2, a dva histološkog gradusa G3, dok je FIGO stadijum u svim slučajevima bio IIIc. U regionu gena BRCA1 LOH je nađen u 5 od 13 slučajeva (38,5%). Od ovih uzoraka četiri su bila histološkog gradusa G2, a jedan histološkog gradusa G3. Po FIGO klasifikaciji jedan uzorak sa LOH bio je u stadijumu Ic, jedan u stadijumu IIIb, dok su tri bila u stadijumu IIIc. Istovremeni gubitak heterozigotnosti za oba ispitivana gena detektovan je u jednom uzorku histološkog gradusa G3, u stadijumu IIIc, što čini 7,7%. Zaključak. Učestalost LOH kod karcinoma ovarijuma iznosila je 30,7% u regionu gena p53, odnosno 38,5% u regionu gena BRCA1. Najveći broj tumora sa LOH bio je histološkog gradusa G2 ili G3, u kliničkom stadijumu IIIc, pa se može zaključiti da je ova pojava povezana sa kasnijom fazom razvoja bolesti.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Analysis of loss of heterozygosity of the tumor suppressor genes p53 and BRCA1 in ovarial carcinomas, Analiza gubitka heterozigotnosti tumor-supresor gena p53 i BRCA1 kod karcinoma ovarijuma",
volume = "63",
number = "9",
pages = "813-818",
doi = "10.2298/VSP0609813P"
}
