An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes
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Peer-reviewed
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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.
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Keywords
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
Journal Title
Nature Genetics
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1061-4036
1546-1718
1546-1718
Volume Title
47
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Springer Nature
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Except where otherwised noted, this item's license is described as All rights reserved
Sponsorship
National Cancer Institute (R01CA129541)
National Cancer Institute (P01CA096832)
Cancer Research UK (22492)
National Cancer Institute (P01CA096832)
Cancer Research UK (22492)
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).