Background: We selected 5 oncogenes with well-established roles in carcinogenesis – CCND1, ErbB1, ErbB2, c-mycand ZNF217– to investigate the coexistence of their copy imbalances in relation to the clinico-pathological characteristics of ovarian tumors. Materials and Methods: Fluorescence in situ hybridization for the 5 genes was applied to a preexisting tissue microarray. 38 ovarian tumors were successfully analyzed for copy number changes of the 5 genes. Results: At least one of these oncogenes was gained/amplified in 27 out of 38 tumors (71.1%). We report the highest frequency of c-mycgenetic gain/amplification since it affected 42.1% of the ovarian tumors. We observed sequential involvement of copy number alterations of the other genes in the presence of c-mycdisruption. The incidence of copy number changes of the 5 oncogenes – both single and combinatorial – was higher in high-grade tumors. All double aberrations in the serous group comprised c-mycand ZNF217copy number increases. Conclusions: Our results revealed a combination between copy number increases of c-mycand ZNF217, associated with serous histology. The data from this combined analysis of the 5 oncogenes could be used as a basis in considering the combined approach in molecular-based therapy of ovarian cancer.

Literature data on the occurrence of CCND1 alterations in ovarian tumors are insufficient. The objective of this study was to assess the incidence of CCND1 copy number changes in a large number of ovarian tumors and its relation to the tumor phenotype: degree of malignancy, histological type, tumor stage, and grade. Fluorescence in situ hybridization (FISH) for analysis of CCND1 copy number changes was applied on a collection of 1 006 ovarian tumors--468 malignant, 48 with low malignant potency, and 490 benign tumors--arranged in tissue microarray. CCND1 amplification was found in 8.46% of the malignant cases and in 8.11% of those with low malignant potency. It was not found in benign ovarian tumors. CCND1 amplification was associated with the mucinous type of ovarian cancer (p<0.0001). CCND1 genetic gain was revealed in 9.06% of the malignant tumors, in 2.70% of the tumors with low malignant potency, and in 4.87% of the benign ovarian tumors. CCND1 gains and amplifications were not associated with the tumor grade and stage. Our results suggest that CCND1 gains are early events in ovarian tumorogenesis.