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Matching mice to malignancy: molecular subgroups and models of medulloblastoma

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Abstract

Introduction

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.

Discussion

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.

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Acknowledgments

We acknowledge support from the Alex’s Lemonade Stand and Pediatric Brain Tumor Foundations and from NIH grants R01CA159859, R01CA133091, R01CA148699, and R01CA122759.

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Authors and Affiliations

  1. Department of Neurology, University of California, San Francisco, CA, USA

    Jasmine Lau, Christin Schmidt & William A. Weiss

  2. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA

    Jasmine Lau, Christin Schmidt & William A. Weiss

  3. Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, CA, USA

    Jasmine Lau, Christin Schmidt & William A. Weiss

  4. Department of Pediatrics, University of California, San Francisco, CA, USA

    Jasmine Lau, Christin Schmidt & William A. Weiss

  5. Tumor Development Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA

    Shirley L. Markant & Robert J. Wechsler-Reya

  6. Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC, USA

    Shirley L. Markant & Robert J. Wechsler-Reya

  7. Division of Neurosurgery, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Michael D. Taylor

  8. Arthur and Sonia Labatt Brain Tumour Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Michael D. Taylor

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  1. Jasmine Lau
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  2. Christin Schmidt
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Correspondence to William A. Weiss.

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Lau, J., Schmidt, C., Markant, S.L. et al. Matching mice to malignancy: molecular subgroups and models of medulloblastoma. Childs Nerv Syst 28, 521–532 (2012). https://doi.org/10.1007/s00381-012-1704-1

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