title: Medulloblastoma stem cells: where development and cancer cross pathways.
abstract: 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.
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Branavan
authors.initials: B
authors.lastname: Manoranjan
authors.forename: Chitra
authors.initials: C
authors.lastname: Venugopal
authors.forename: Nicole
authors.initials: N
authors.lastname: McFarlane
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Doble
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Dunn
authors.forename: Katrin
authors.initials: K
authors.lastname: Scheinemann
authors.forename: Sheila K
authors.initials: SK
authors.lastname: Singh
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002528:Cerebellar Neoplasms / Q000503:physiopathology*; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism; D002648:Child; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008527:Medulloblastoma / Q000503:physiopathology*; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000502:physiology*; D010372:Pediatrics / Q000379:methods* / Q000639:trends; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D051153:Wnt Proteins