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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Chromosome Aberrations
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DNA Copy Number Variations
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Ependymoma / genetics*
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Ependymoma / metabolism
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Female
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Genes, Tumor Suppressor*
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Genetic Predisposition to Disease / genetics*
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HEK293 Cells
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Humans
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Kaplan-Meier Estimate
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Male
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Mice, Nude
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Mice, Transgenic
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Microscopy, Confocal
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / metabolism
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Neural Stem Cells / metabolism
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Neural Stem Cells / transplantation
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Oligonucleotide Array Sequence Analysis
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Oncogenes / genetics*
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Reverse Transcriptase Polymerase Chain Reaction
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Transfection