10.17863/CAM.10310
Mohankumar, KM
Currle, DS
White, E
Boulos, N
Dapper, J
Eden, C
Nimmervoll, Birgit
0000-0002-3324-092X
Thiruvenkatam, R
Connelly, M
Kranenburg, TA
Neale, G
Olsen, S
Wang, Y-D
Finkelstein, D
Wright, K
Gupta, K
Ellison, DW
Thomas, AO
Gilbertson, Richard
0000-0001-7539-9472
An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes
Apollo - University of Cambridge Repository (staging)
2015
Animals
Cells, Cultured
Chromosome Aberrations
DNA Copy Number Variations
Ependymoma
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Genetic Predisposition to Disease
HEK293 Cells
Humans
Kaplan-Meier Estimate
Male
Mice, Nude
Mice, Transgenic
Microscopy, Confocal
Neoplasms, Experimental
Neural Stem Cells
Oligonucleotide Array Sequence Analysis
Oncogenes
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Apollo - University of Cambridge Repository (staging)
Apollo - University of Cambridge Repository (staging)
2015-08
Article
1061-4036
1546-1718
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.
We are grateful to F.B. Gertler (Massachusetts Institute of Technology) and S. Gupton (University of North Carolina) for the generous gift of the VAMP7-phlorin construct and the staffs of the Hartwell Center for Bioinformatics and Biotechnology, the Small Animal Imaging Center, the Animal Resources Center, the Cell and Tissue Imaging Center, and the Flow Cytometry and Cell Sorting Shared Resource at St. Jude Children's Research Hospital for technical assistance. This work was supported by grants from the US National Institutes of Health (R01CA129541, P01CA96832 and P30CA021765, R.J.G.), by the Collaborative Ependymoma Research Network (CERN) and by the American Lebanese Syrian Associated Charities (ALSAC).