In vivo oncogenomics screen identifies novel ependymoma oncogenes and tumor suppressor genes within large chromosomal alterations

Cancers are characterized by non-random, chromosome copy number variations 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 11 TSGs that dysregulate a small number of cell functions including vesicle trafficking and cholesterol biosynthesis; pinpointing these as potential points for therapeutic intervention. Mouse cortical tumors were excised. These tumors derived from cells expressing one of 3 genes: RAB3A, BC74C, or ZNF668