[Analysis of loss of heterozygosity of the tumor suppressor genes p53 and BRCA1 in ovarial carcinomas].
OBJECTIVE
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 IlIc. LOH in both of the analyzed regions was detected in one tumor (7.70), with histological gradus G3 and the FIGO IIIc stage.


CONCLUSIONS
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.
Petrović
Bojana
B
Klinicki centar Srbije, Institut za ginekologiju i akuserstvo, Beograd.
Perović
Milica
M
Novaković
Ivana
I
Atanacković
Jasmina
J
Popović
Branka
B
Luković
Ljiljana
L
Petković
Spasoje
S
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis