Abstract
Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor. Recent advances in sequencing technologies have revolutionized molecular classification of these highly aggressive tumors. MB is divided into 4 molecular subgroups that exhibit different genomic alterations, gene expression profiles, response to treatment, and developmental cell of origin: WNT, Sonic Hedgehog (SHH), Group 3, and Group 4. Additional stratification into as many as 14 molecular subtypes underscores the extensive heterogeneity and complexity both between and within the major subgroups. While targeted therapies are being evaluated, the current treatment for MB still consists of aggressive surgery, high doses of cytotoxic chemotherapy, and radiation to the whole brain and spinal cord. These treatments do not take into account the extensive heterogeneity between and within MB subgroups. Cancer stem cells also play an important role in treatment failure and recurrence in MB, adding an additional layer of complexity in the form of cellular heterogeneity. This chapter will focus on the clinical presentation of MB, current treatment options including proton-based radiotherapy, histological classifications, and a detailed description of the current molecular subgroups and subtypes, followed by exploration of cellular heterogeneity in the molecular era. Further dissection of tumor heterogeneity and identification of subgroup and subtype-specific biomarkers will be crucial in the development of novel diagnostic markers and targeted therapies for these highly aggressive pediatric brain tumors.KeywordsPosterior fossa tumorsMedulloblastomaPediatricTumor heterogeneityCancer stem cell
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