Association of overexpressed MYC gene with altered PHACTR3 and E2F4 genes contributes to non-small cell lung carcinoma pathogenesis

Background: C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the genes previously identified to be related to NSCLC pathogenesis, PHACTR3 and E2F4. Methods: We analyzed MYC gene expression by qRT-PCR in 30 NSCLC patients' samples and paired normal lung tissue. MYC expression was further statistically evaluated in relation to histopathological parameters, PHACTR3 and E2F4 gene alterations and survival. Alterations in aforementioned genes were previously detected and identified based on AP-PCR profiles of paired normal and tumor DNA samples, selection of DNA bands with altered mobility in tumor samples and their characterization by the reamplification, cloning and sequencing. Rezultati: Ekspresija gena MYC je povecana u uzorcima NSCLC i predstavlja znacajnu karakteristiku karcinoma skvamoznih celija. Prekomerna ekspresija ovog gena asocira sa prisustvom mutacija u genima PHACTR3 i E2F4 u celoj grupi pacijenata, kao i u podgrupi karcinoma skvamoznih celija. Takođe, pacijenti sa povecanom ekspresijom MYC gena i istovremeno mutiranim PHACTR3 ili E2F4 genima su pokazali trend kraceg preživljavanja. Conclusions: Overall, MYC is frequently overexpressed in NSCLC and it is associated with mutated PHACTR3 gene, as well as mutated E2F4 gene. These joint gene alterations could be considered as potential molecular markers of NSCLC and its specific subtypes.