Medulloblastoma is the most common malignant cerebellar tumor in children. Recent technological advances in multi-layered omics data analysis have revealed four molecular subgroups of medulloblastoma (Wingless/int, Sonic hedgehog, Group3 and Group4). (Epi)genomic and transcriptomic profiling on human primary medulloblastomas show distinct oncogenic drivers and cellular origin(s) across the subgroups. Despite tremendous efforts to identify the molecular signals driving tumorigenesis, few of the identified targets are druggable; therefore, further understanding of the etiology of tumors is required to establish effective molecular targeted therapies. Chromatin regulators are frequently mutated in medulloblastoma, prompting us to investigate epigenetic alterations and the accompanying activation of oncogenic signaling during tumorigenesis. For this purpose, we use germline and non-germline genetically engineered mice to model human medulloblastoma and to generate useful, molecularly-targeted, preclinical studies. This review discusses the biological implications of chromatin regulator mutations during medulloblastoma pathogenesis, based on recent in vivo animal studies.
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