Matching mice to malignancy: molecular subgroups and models of medulloblastoma

Medulloblastoma, the largest group of embryonal brain tumors, has historically been classified into five variants based on histopathology. More recently, epigenetic and transcriptional analyses of primary tumors have subclassified medulloblastoma into four to six subgroups, most of which are incongruous with histopathological classification.

Improved stratification is required for prognosis and development of targeted treatment strategies, to maximize cure and minimize adverse effects. Several mouse models of medulloblastoma have contributed both to an improved understanding of progression and to developmental therapeutics. In this review, we summarize the classification of human medulloblastoma subtypes based on histopathology and molecular features. We describe existing genetically engineered mouse models, compare these to human disease, and discuss the utility of mouse models for developmental therapeutics. Just as accurate knowledge of the correct molecular subtype of medulloblastoma is critical to the development of targeted therapy in patients, we propose that accurate modeling of each subtype of medulloblastoma in mice will be necessary for preclinical evaluation and optimization of those targeted therapies.