The neuroblastoma 17q enigma: exploiting zebrafish modeling to study the cooperative role of 17q genes in MYCN driven tumor formation

Neuroblastoma is a neuronal childhood tumor that accounts for 15% of childhood cancer mortality.
The search for more effective and less toxic therapeutic options remains one of the most
challenging tasks in cancer research. The most frequent aberration in neuroblastoma is the gain of chromosome 17q. Until now, it remained unclear which genes on 17q are responsible for neuroblastoma development. Using several bioinformatics approaches, we generated a list of top candidates. Highest ranked was BIRC5, a gene strongly correlated with survival and implicated in many other cancers. Furthermore, we also selected three highly transcriptionally upregulated 17q genes implicated in replicative stress, i.e. BRIP1, BRCA1 and TOP2A. In this project, we will test the cooperative effect of these four selected genes in MYCN transgenic zebrafish lines through monitoring of acceleration of MYCN driven tumor formation. With this study, we will better understand the complex cooperative genetic process of 17q gain in MYCN driven tumor formation.
Moreover, we will take advantage of these more complex genetic models, which closer resemble the human disease, for the testing of novel anticancer drug combinations.