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  • An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes.

An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes.

Nature genetics (2015-06-16)
Kumarasamypet M Mohankumar, David S Currle, Elsie White, Nidal Boulos, Jason Dapper, Christopher Eden, Birgit Nimmervoll, Radhika Thiruvenkatam, Michele Connelly, Tanya A Kranenburg, Geoffrey Neale, Scott Olsen, Yong-Dong Wang, David Finkelstein, Karen Wright, Kirti Gupta, David W Ellison, Arzu Onar Thomas, Richard J Gilbertson
ABSTRACT

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.