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

Nat Genet. 2015 Aug;47(8):878-87. doi: 10.1038/ng.3323. Epub 2015 Jun 15.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromosome Aberrations
  • DNA Copy Number Variations
  • Ependymoma / genetics*
  • Ependymoma / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Genetic Predisposition to Disease / genetics*
  • HEK293 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice, Nude
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / transplantation
  • Oligonucleotide Array Sequence Analysis
  • Oncogenes / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Associated data

  • GEO/GSE67497