Medulloblastoma (MB) is the most common childhood malignant brain tumor, accounting for approximately 20% of all pediatric central nervous system tumors. Current standard treatments involving surgical interventions followed by craniospinal irradiation and adjuvant chemotherapy have severe motor and cognitive defects. Therefore, individualized treatment regimens with reduced toxicity designed according to the presence of specific oncogenic ‘driver’ genes are urgently demanded. To this end, recent genetic and epigenetic findings have advanced the classification of MB into the international consensus of four distinct MB molecular subgroups (WNT, SHH, Group 3, and Group 4) based on their respective molecular and histopathological characteristics. More recent studies have indicated that up to seven molecular subgroups exist in childhood MB. Moreover, studies on the inter- and intra-tumoral features of the four subgroups revealed that each subgroup contains variant subtypes. These results have greatly helped risk stratification of MB patients at diagnosis and significantly improved clinical treatment options. Herein, we highlight the recent advances and challenges associated with MB classification, and the development of therapeutic treatments targeting novel subgroup-specific molecular and epigenetic factors, especially those in the SHH-driven MB tumors.Copyright © 2020. Published by Elsevier Inc.
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