title: 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.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Kumarasamypet M
authors.initials: KM
authors.lastname: Mohankumar
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Currle
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Elsie
authors.initials: E
authors.lastname: White
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Nidal
authors.initials: N
authors.lastname: Boulos
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Dapper
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Eden
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Birgit
authors.initials: B
authors.lastname: Nimmervoll
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Radhika
authors.initials: R
authors.lastname: Thiruvenkatam
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Connelly
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Tanya A
authors.identifier: 0000000253294968
authors.initials: TA
authors.lastname: Kranenburg
authors.affiliation: Hartwell Center for Biotechnology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Neale
authors.affiliation: Hartwell Center for Biotechnology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Olsen
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Yong-Dong
authors.initials: YD
authors.lastname: Wang
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: David
authors.initials: D
authors.lastname: Finkelstein
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Wright
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Kirti
authors.initials: K
authors.lastname: Gupta
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Arzu Onar
authors.initials: AO
authors.lastname: Thomas
authors.affiliation: 1] Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbertson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D004806:Ependymoma / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008819:Mice, Nude; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection