KM Mohankumar, DS Currle, E White, N Boulos, J Dapper, C Eden, B Nimmervoll, R Thiruvenkatam, M Connelly, TA Kranenburg, G Neale, S Olsen, Y-D Wang, D Finkelstein, K Wright, K Gupta, DW Ellison, AO Thomas, RJ Gilbertson
Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.