Medulloblastoma Can Be Initiated by Deletion of Patched in Lineage-Restricted Progenitors or Stem Cells

Zeng Jie Yang, Tammy Ellis, Shirley L. Markant, Tracy Ann Read, Jessica D. Kessler, Melissa Bourboulas, Ulrich Schüller, Robert Machold, Gordon Fishell, David H. Rowitch, Brandon J. Wainwright, Robert J. Wechsler-Reya

Research output: Contribution to journalArticle

Abstract

Medulloblastoma is the most common malignant brain tumor in children, but the cells from which it arises remain unclear. Here we examine the origin of medulloblastoma resulting from mutations in the Sonic hedgehog (Shh) pathway. We show that activation of Shh signaling in neuronal progenitors causes medulloblastoma by 3 months of age. Shh pathway activation in stem cells promotes stem cell proliferation but only causes tumors after commitment to-and expansion of-the neuronal lineage. Notably, tumors initiated in stem cells develop more rapidly than those initiated in progenitors, with all animals succumbing by 3-4 weeks. These studies suggest that medulloblastoma can be initiated in progenitors or stem cells but that Shh-induced tumorigenesis is associated with neuronal lineage commitment.

Original languageEnglish (US)
Pages (from-to)135-145
Number of pages11
JournalCancer Cell
Volume14
Issue number2
DOIs
StatePublished - Aug 12 2008

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Medulloblastoma
Hedgehogs
Stem Cells
Brain Neoplasms
Neoplasms
Carcinogenesis
Cell Proliferation
Mutation

Keywords

  • CELLBIO
  • HUMDISEASE
  • STEMCELL

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Yang, Z. J., Ellis, T., Markant, S. L., Read, T. A., Kessler, J. D., Bourboulas, M., ... Wechsler-Reya, R. J. (2008). Medulloblastoma Can Be Initiated by Deletion of Patched in Lineage-Restricted Progenitors or Stem Cells. Cancer Cell, 14(2), 135-145. https://doi.org/10.1016/j.ccr.2008.07.003

Medulloblastoma Can Be Initiated by Deletion of Patched in Lineage-Restricted Progenitors or Stem Cells. / Yang, Zeng Jie; Ellis, Tammy; Markant, Shirley L.; Read, Tracy Ann; Kessler, Jessica D.; Bourboulas, Melissa; Schüller, Ulrich; Machold, Robert; Fishell, Gordon; Rowitch, David H.; Wainwright, Brandon J.; Wechsler-Reya, Robert J.

In: Cancer Cell, Vol. 14, No. 2, 12.08.2008, p. 135-145.

Research output: Contribution to journalArticle

Yang, ZJ, Ellis, T, Markant, SL, Read, TA, Kessler, JD, Bourboulas, M, Schüller, U, Machold, R, Fishell, G, Rowitch, DH, Wainwright, BJ & Wechsler-Reya, RJ 2008, 'Medulloblastoma Can Be Initiated by Deletion of Patched in Lineage-Restricted Progenitors or Stem Cells', Cancer Cell, vol. 14, no. 2, pp. 135-145. https://doi.org/10.1016/j.ccr.2008.07.003
Yang, Zeng Jie ; Ellis, Tammy ; Markant, Shirley L. ; Read, Tracy Ann ; Kessler, Jessica D. ; Bourboulas, Melissa ; Schüller, Ulrich ; Machold, Robert ; Fishell, Gordon ; Rowitch, David H. ; Wainwright, Brandon J. ; Wechsler-Reya, Robert J. / Medulloblastoma Can Be Initiated by Deletion of Patched in Lineage-Restricted Progenitors or Stem Cells. In: Cancer Cell. 2008 ; Vol. 14, No. 2. pp. 135-145.
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