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Medulloblastoma stem cells: where development and cancer cross pathways

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PEDIATRIC RESEARCH
卷 71, 期 4, 页码 516-522

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NATURE PUBLISHING GROUP
DOI: 10.1038/pr.2011.62

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  1. Department of Surgery at McMaster University
  2. Ontario Institute for Cancer Research
  3. JP Bickell Foundation
  4. Stem Cell Network
  5. Canadian Institutes of Health Research

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Brain tumors are the leading cause of childhood cancer mortality, with medulloblastoma (MB) representing the most frequent malignant tumor. The recent molecular classification of MB has reconceptualized the heterogeneity that exists within pathological subtypes by giving context to the role of key developmental signaling pathways in MB pathogenesis. The identification of cancer stem cell (CSC) populations, termed brain tumor-initiating cells (BTICs), in MB has provided novel cellular targets for the study of these aberrantly activated signaling pathways, namely, Sonic hedgehog (Shh) and Wingless (Wnt), along with the identification of novel BTIC self-renewal pathways. In this review, we discuss recent evidence for the presence of a MB stem cell that drives tumorigenesis in this malignant childhood tumor. We focus on evidence from cerebellar development, the recent identification of BTICs, the presence of activated developmental signaling pathways in MB, the role of epigenetic stem cell regulatory mechanisms, and how these developmental and epigenetic pathways may be targeted for novel therapeutic options.

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