An animal model of MYC-driven medulloblastoma

Summary 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 how that cere...

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Hauptverfasser: Pei, Yanxin (VerfasserIn) , Witt, Hendrik (VerfasserIn) , Korshunov, Andrey (VerfasserIn) , Pfister, Stefan (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: February 13, 2012
In: Cancer cell
Year: 2012, Jahrgang: 21, Heft: 2, Pages: 155-167
ISSN:1878-3686
DOI:10.1016/j.ccr.2011.12.021
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1016/j.ccr.2011.12.021
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1535610811004831
Volltext
Verfasserangaben:Yanxin Pei, Colin E. Moore, Jun Wang, Alok K. Tewari, Alexey Eroshkin, Yoon-Jae Cho, Hendrik Witt, Andrey Korshunov, Tracy-Ann Read, Julia L. Sun, Earlene M. Schmitt, C. Ryan Miller, Anne F. Buckley, Roger E. McLendon, Thomas F. Westbrook, Paul A. Northcott, Michael D. Taylor, Stefan M. Pfister, Phillip G. Febbo and Robert J. Wechsler-Reya

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520 |a Summary 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 how 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. 
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