Cross-species genomics identifies postanatal CPE as novel choroid plexus carcinoma oncogenes

Choroid plexus carcinomas (CPC) are poorly understood and frequently lethal brain tumors with minimal treatment options. Using a new mouse model of the disease and a large cohort of human CPCs [GSE60892; GSE60899], we performed a cross-species, genome-wide search for novel oncogenes within syntenic regions of chromosome gain. TAF12, NFYC and RAD54L, co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3, were identified as oncogenes that are gained in tumors in both species and required to initiate and progress the disease in mice. TAF12 and NFYC are transcription factors that regulate the epigenome, while RAD54L plays a central role in DNA repair. Our data identify a group of concurrently gained, novel oncogenes that cooperate in the formation of CPC and unmask potential new avenues for therapy. CPC mouse model samples of tumors derived from choroid plexus epithelium (CPE) cells that are Tp53/RB/Pten null in FVB mice. Female CD1 nude (host) mice were transfected with postanatal CPE and compared with a medulloblastoma normal mouse embryonic, postnatal and adult controls (loxP TP53/RB/PTEN (no Cre)) Implanted and reimplanted are from the orthotropic transplants of the primary tumor or later tumors