∼ 30 % of Neuroblastoma harbor amplifications of the MYCN oncogene, which is the strongest molecular marker of poor prognosis. However, a subset of high-risk neuroblastoma does not carry alterations of the MYCN gene and the molecular pathways underlying their aggressive behavior remains to be elucidated. We have utilized a functional genomics approach with both genetically defined cell systems, as well as molecularly defined neuroblastoma cell lines, to identify critical survival pathways that distinguish MYCN-amplified versus non-amplified neuroblastoma. The results of high throughput siRNA screens targeting the druggable genome will be presented and discussed in light of public microarray data and validation experiments carried out in our laboratory. These findings revealed that different chromatin-remodeling genes, DNA-repair and developmental pathways differentiate MYCN amplified neuroblastoma versus non-amplified, thus highlighting specific new therapeutic targets associated with MYCN status as well as other molecular markers. In addition to pinpointing novel therapeutic targets for high-risk neuroblastoma, our study also functional defines signaling pathways activated in high-risk neruoblastoma and could be utilized to guide rational therapeutic choices.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5139. doi:1538-7445.AM2012-5139