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 journalArticle

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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

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Medulloblastoma
Animal Models
Neoplasms
Stem Cells
Animal Disease Models
Phosphatidylinositol 3-Kinases
Oncogenes
Brain Neoplasms
Transplantation
Growth
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Pei, Y., Moore, C. E., Wang, J., Tewari, A. K., Eroshkin, A., Cho, Y-J., ... Wechsler-Reya, R. J. (2012). An Animal Model of MYC-Driven Medulloblastoma. Cancer Cell, 21(2), 155-167. https://doi.org/10.1016/j.ccr.2011.12.021

An Animal Model of MYC-Driven Medulloblastoma. / Pei, Yanxin; Moore, Colin E.; Wang, Jun; Tewari, Alok K.; Eroshkin, Alexey; Cho, Yoon-Jae; Witt, Hendrik; Korshunov, Andrey; Read, Tracy Ann; Sun, Julia L.; Schmitt, Earlene M.; Miller, C. Ryan; Buckley, Anne F.; McLendon, Roger E.; Westbrook, Thomas F.; Northcott, Paul A.; Taylor, Michael D.; Pfister, Stefan M.; Febbo, Phillip G.; Wechsler-Reya, Robert J.

In: Cancer Cell, Vol. 21, No. 2, 14.02.2012, p. 155-167.

Research output: Contribution to journalArticle

Pei, Y, Moore, CE, Wang, J, Tewari, AK, Eroshkin, A, Cho, Y-J, Witt, H, Korshunov, A, Read, TA, Sun, JL, Schmitt, EM, Miller, CR, Buckley, AF, McLendon, RE, Westbrook, TF, Northcott, PA, Taylor, MD, Pfister, SM, Febbo, PG & Wechsler-Reya, RJ 2012, 'An Animal Model of MYC-Driven Medulloblastoma', Cancer Cell, vol. 21, no. 2, pp. 155-167. https://doi.org/10.1016/j.ccr.2011.12.021
Pei Y, Moore CE, Wang J, Tewari AK, Eroshkin A, Cho Y-J et al. An Animal Model of MYC-Driven Medulloblastoma. Cancer Cell. 2012 Feb 14;21(2):155-167. https://doi.org/10.1016/j.ccr.2011.12.021
Pei, Yanxin ; Moore, Colin E. ; Wang, Jun ; Tewari, Alok K. ; Eroshkin, Alexey ; Cho, Yoon-Jae ; Witt, Hendrik ; Korshunov, Andrey ; Read, Tracy Ann ; Sun, Julia L. ; Schmitt, Earlene M. ; Miller, C. Ryan ; Buckley, Anne F. ; McLendon, Roger E. ; Westbrook, Thomas F. ; Northcott, Paul A. ; Taylor, Michael D. ; Pfister, Stefan M. ; Febbo, Phillip G. ; Wechsler-Reya, Robert J. / An Animal Model of MYC-Driven Medulloblastoma. In: Cancer Cell. 2012 ; Vol. 21, No. 2. pp. 155-167.
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