title: An animal model of MYC-driven medulloblastoma.
abstract: Medulloblastoma (MB) is the most common malignant brain tumor in children. Patients whose tumors exhibit overexpression or amplification of the MYC oncogene (c-MYC) usually have an extremely poor prognosis, but there are no animal models of this subtype of the disease. Here, we show that cerebellar stem cells expressing Myc and mutant Trp53 (p53) generate aggressive tumors following orthotopic transplantation. These tumors consist of large, pleiomorphic cells and resemble human MYC-driven MB at a molecular level. Notably, antagonists of PI3K/mTOR signaling, but not Hedgehog signaling, inhibit growth of tumor cells. These findings suggest that cerebellar stem cells can give rise to MYC-driven MB and identify a novel model that can be used to test therapies for this devastating disease.
authors.affiliation: Tumor Development Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Pei
authors.forename: Colin E
authors.initials: CE
authors.lastname: Moore
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Alok K
authors.initials: AK
authors.lastname: Tewari
authors.forename: Alexey
authors.initials: A
authors.lastname: Eroshkin
authors.forename: Yoon-Jae
authors.initials: YJ
authors.lastname: Cho
authors.forename: Hendrik
authors.initials: H
authors.lastname: Witt
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.forename: Tracy-Ann
authors.initials: TA
authors.lastname: Read
authors.forename: Julia L
authors.initials: JL
authors.lastname: Sun
authors.forename: Earlene M
authors.initials: EM
authors.lastname: Schmitt
authors.forename: C Ryan
authors.initials: CR
authors.lastname: Miller
authors.forename: Anne F
authors.initials: AF
authors.lastname: Buckley
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Westbrook
authors.forename: Paul A
authors.initials: PA
authors.lastname: Northcott
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Febbo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wechsler-Reya
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D008527:Medulloblastoma / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D058953:Neural Stem Cells / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology
chemical_list: D000631:Aminopyridines; D007093:Imidazoles; D009025:Morpholines; C571178:NVP-BKM120; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D011804:Quinolines; D058570:TOR Serine-Threonine Kinases; C531198:dactolisib