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

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.

• Authors: 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
• Journal: Nature genetics (Nat Genet) Vol. 47 Issue 8 Pg. 878-87 (Aug 2015) ISSN: 1546-1718 [Electronic] United States
• PMID: 26075792 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Cells, Cultured
• Chromosome Aberrations
• DNA Copy Number Variations
• Ependymoma (genetics, 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, metabolism)
• Neural Stem Cells (metabolism, transplantation)
• Oligonucleotide Array Sequence Analysis
• Oncogenes (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection