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Medulloblastoma Stem Cells

Xing Fan, Charles G. Eberhart

From the Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD

Corresponding author: Xing Fan, MD, PhD, Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Pl, 5018 BSRB, Ann Arbor, MI 48109-2200; e-mail: xingf{at}med.umichu.edu; or Charles G. Eberhart, MD, PhD, Johns Hopkins University School of Medicine, Department of Pathology, 720 Rutland Ave, Ross Building 558, Baltimore, MD 21205; e-mail: ceberha{at}jhmi.edu

Medulloblastoma and other embronal brain tumors are similar in appearance and differentiation potential to neural stem and progenitor cells. Expression studies performed using human tumor samples, as well as the analysis of murine transgenic models, suggest that both multipotent cerebellar stem cells and lineage-restricted progenitors of the external germinal layer can be transformed into medulloblastoma by genetic alterations. These molecular changes frequently involve constitutive activation of signaling pathways such as Wnt, Hedgehog, and Notch, which play a key role in non-neoplastic neural stem cells. Pharmacologic blockade of the Hedgehog and Notch pathways suppresses the growth of medulloblastoma in culture and in vivo and may prove effective in targeting the small cancer stem-cell subpopulation required for tumor initiation and long-term propagation.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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