Skip to main content
Journal cover image

Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma.

Publication ,  Journal Article
Oliver, TG; Read, TA; Kessler, JD; Mehmeti, A; Wells, JF; Huynh, TTT; Lin, SM; Wechsler-Reya, RJ
Published in: Development
May 2005

Medulloblastoma is the most common malignant brain tumor in children. It is thought to result from the transformation of granule cell precursors (GCPs) in the developing cerebellum, but little is known about the early stages of the disease. Here, we identify a pre-neoplastic stage of medulloblastoma in patched heterozygous mice, a model of the human disease. We show that pre-neoplastic cells are present in the majority of patched mutants, although only 16% of these mice develop tumors. Pre-neoplastic cells, like tumor cells, exhibit activation of the Sonic hedgehog pathway and constitutive proliferation. Importantly, they also lack expression of the wild-type patched allele, suggesting that loss of patched is an early event in tumorigenesis. Although pre-neoplastic cells resemble GCPs and tumor cells in many respects, they have a distinct molecular signature. Genes that mark the pre-neoplastic stage include regulators of migration, apoptosis and differentiation, processes crucial for normal development but previously unrecognized for their role in medulloblastoma. The identification and molecular characterization of pre-neoplastic cells provides insight into the early steps in medulloblastoma formation, and may yield important markers for early detection and therapy of this disease.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Development

DOI

ISSN

0950-1991

Publication Date

May 2005

Volume

132

Issue

10

Start / End Page

2425 / 2439

Location

England

Related Subject Headings

  • Stem Cells
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Cell Surface
  • Precancerous Conditions
  • Patched Receptors
  • Mutation
  • Microarray Analysis
  • Mice
  • Membrane Proteins
  • Medulloblastoma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Oliver, T. G., Read, T. A., Kessler, J. D., Mehmeti, A., Wells, J. F., Huynh, T. T. T., … Wechsler-Reya, R. J. (2005). Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma. Development, 132(10), 2425–2439. https://doi.org/10.1242/dev.01793
Oliver, Trudy G., Tracy Ann Read, Jessica D. Kessler, Anriada Mehmeti, Jonathan F. Wells, Trang T. T. Huynh, Simon M. Lin, and Robert J. Wechsler-Reya. “Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma.Development 132, no. 10 (May 2005): 2425–39. https://doi.org/10.1242/dev.01793.
Oliver TG, Read TA, Kessler JD, Mehmeti A, Wells JF, Huynh TTT, et al. Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma. Development. 2005 May;132(10):2425–39.
Oliver, Trudy G., et al. “Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma.Development, vol. 132, no. 10, May 2005, pp. 2425–39. Pubmed, doi:10.1242/dev.01793.
Oliver TG, Read TA, Kessler JD, Mehmeti A, Wells JF, Huynh TTT, Lin SM, Wechsler-Reya RJ. Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma. Development. 2005 May;132(10):2425–2439.
Journal cover image

Published In

Development

DOI

ISSN

0950-1991

Publication Date

May 2005

Volume

132

Issue

10

Start / End Page

2425 / 2439

Location

England

Related Subject Headings

  • Stem Cells
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Cell Surface
  • Precancerous Conditions
  • Patched Receptors
  • Mutation
  • Microarray Analysis
  • Mice
  • Membrane Proteins
  • Medulloblastoma