Medulloblastoma stem cells: Modeling tumor heterogeneity

Brain tumors represent the leading cause of childhood cancer mortality, with medulloblastoma (MB) being the most frequent malignant tumor. In this review we discuss the morphological and molecular heterogeneity of this malignant childhood brain tumor and how this key feature has implicated the presence of a MB stem cell. We focus on evidence from cerebellar development, histopathological and molecular subtypes of MB, the recent identification of brain tumor-initiating cells (BTICs, also referred to as MB stem cells), and the current limitations in studying the interplay between MB stem cells and tumor heterogeneity.

► MB molecular subtype-specific cells of origin show spatial and intratumoral heterogeneity.
► Cell populations in developing cerebellum contain MB cells of origin.
► Cancer stem cell hypothesis and BTICs are ideal model systems for studying MB heterogeneity.