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Genetic and molecular alterations across medulloblastoma subgroups

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Abstract

Medulloblastoma is the most common malignant brain tumour diagnosed in children. Over the last few decades, advances in radiation and chemotherapy have significantly improved the odds of survival. Nevertheless, one third of all patients still succumb to their disease, and many long-term survivors are afflicted with neurocognitive sequelae. Large-scale multi-institutional efforts have provided insight into the transcriptional and genetic landscape of medulloblastoma. Four distinct subgroups of medulloblastoma have been identified, defined by distinct transcriptomes, genetics, demographics and outcomes. Integrated genomic profiling of each of these subgroups has revealed distinct genetic alterations, driving pathways and in some instances cells of origin. In this review, we highlight, in a subgroup-specific manner, our current knowledge of the genetic and molecular alterations in medulloblastoma and underscore the possible avenues for future therapeutic intervention.

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Acknowledgments

MDT is funded by the Canadian Institutes of Health Research, National Institutes of Health (R01CA159859 and R01CA148699), Pediatric Brain Tumor Foundation, he is the Garron Family Chair in Childhood Cancer Research at The Hospital for Sick Children and The University of Toronto. VR is supported by a Canadian Institutes of Health Research fellowship, AIHS Clinical Fellowship and ALSF Young Investigator award. PS is funded through Natural Sciences and Engineering Research Council of Canada (NSERC), University of Toronto, and the Research Training Competition (RESTRACOMP) at The Hospital for Sick Children.

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Authors and Affiliations

  1. Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada

    Patryk Skowron, Vijay Ramaswamy & Michael D. Taylor

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Patryk Skowron & Michael D. Taylor

  3. Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada

    Vijay Ramaswamy

  4. Division of Neurosurgery, The Hospital for Sick Children, 555, University Avenue, Toronto, Ontario, M5G 1X8, Canada

    Michael D. Taylor

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Skowron, P., Ramaswamy, V. & Taylor, M.D. Genetic and molecular alterations across medulloblastoma subgroups. J Mol Med 93, 1075–1084 (2015). https://doi.org/10.1007/s00109-015-1333-8

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