doiSerbia

Alterations of c-Myc and c-erbB-2 genes in ovarian tumours

Pastor Tibor (Institut za sudsku medicinu, Stomatološki fakultet, Beograd)
Popović Branka (Institut za sudsku medicinu, Stomatološki fakultet, Beograd)
Gvozdenović Ana (Institut za sudsku medicinu, Stomatološki fakultet, Beograd)
Boro Aleksandar (Institut za sudsku medicinu, Stomatološki fakultet, Beograd)
Petrović Bojana (Institut za ginekologiju i akušerstvo, Klinički centar Srbije, Beograd)
Novaković Ivana (Institut za humanu genetiku, Medicinski fakultet, Beograd)
Puzović Dragana (Institut za sudsku medicinu, Stomatološki fakultet, Beograd)
Luković Ljiljana (Institut za humanu genetiku, Medicinski fakultet, Beograd)
Milašin Jelena (Institut za sudsku medicinu, Stomatološki fakultet, Beograd)

Introduction. According to clinical and epidemiological studies, ovarian cancer ranks fifth in cancer deaths among women. The causes of ovarian cancer remain largely unknown but various factors may increase the risk of developing it, such as age, family history of cancer, childbearing status etc. This cancer results from a succession of genetic alterations involving oncogenes and tumour suppressor genes, which have a critical role in normal cell growth regulation. Mutations and/or overexpression of three oncogenes, c-erbB-2, c-Myc and K-ras, and of the tumour suppressor gene p53, have been frequently observed in a sporadic ovarian cancer. Objective. The aim of the present study was to analyze c-Myc and c-erbB-2 oncogene alterations, specifically amplification, as one of main mechanisms of their activation in ovarian cancers and to establish a possible association with the pathogenic process. Methods. DNA was isolated from 15 samples of malignant and 5 benign ovarian tumours, using proteinase K digestion, followed by phenol-chloroform isoamyl extraction and ethanol precipitation. C-Myc and c-erbB-2 amplification were detected by differential PCR. The level of gene copy increase was measured using the Scion image software. Results. The amplification of both c-Myc and c-erbB-2 was detected in 26.7% of ovarian epithelial carcinoma specimens. Only one tumour specimen concomitantly showed increased gene copy number for both studied genes. Interestingly, besides amplification, gene deletion was also detected (26.7% for c-erbB-2). Most of the ovarian carcinomas with alterations in c-Myc and c-erbB-2 belonged to advanced FIGO stages. Conclusion. The amplification of c-Myc and c-erbB-2 oncogenes in ovarian epithelial carcinomas is most probably a late event in the pathogenesis conferring these tumours a more aggressive biological behaviour. Similarly, gene deletions point to genomic instability in epithelial carcinomas in higher clinical stages as the result of clonal evolution and selection.

Keywords: c-Myc oncogene amplification, c-erbB-2 oncogene amplification, dPCR, ovarian tumours