An Animal Model of MYC-Driven Medulloblastoma

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, Robert J. Wechsler-Reya

Research output: Contribution to journalArticlepeer-review

241 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)155-167
Number of pages13
JournalCancer Cell
Volume21
Issue number2
DOIs
StatePublished - Feb 14 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'An Animal Model of MYC-Driven Medulloblastoma'. Together they form a unique fingerprint.

Cite this