Abstract
Medulloblastoma, the most common malignant paediatric brain tumour, is currently diagnosed and stratified using a combination of clinical and demographic variables. Recent transcriptomic approaches have demonstrated that the histological entity known as medulloblastoma is comprised of multiple clinically and molecularly distinct subgroups. The current consensus is that four defined subgroups of medulloblastoma exist: WNT, SHH, Group 3, and Group 4. Each subgroup probably contains at least one additional level of hierarchy, with some evidence for multiple subtypes within each subgroup. The demographic and clinical differences between the subgroups present immediate and pressing questions to be addressed in the next round of clinical trials for patients with medulloblastoma. Many of the genetically defined targets for rational medulloblastoma therapies are unique to a given subgroup, suggesting the need for subgroup-specific trials of novel therapies. The development of practical, robust and widely accepted subgroup biomarkers that are amenable to the conditions of a prospective clinical trial is, therefore, an urgent need for the paediatric neuro-oncology community. In this Review, we discuss the clinical implications of molecular subgrouping in medulloblastoma, highlighting how these subgroups are transitioning from a research topic in the laboratory to a clinically relevant topic with important implications for patient care.
Key Points
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Medulloblastoma is no longer regarded as a single disease: at least four main subgroups—WNT, SHH, Group 3, and Group 4—are now accepted to exist
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Each subgroup of medulloblastoma exhibits distinct patient demographics, underlying genomics, and transcriptomics, which leads to disparate clinical presentation
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Patient subgroup status will become an integral component of prospective clinical trials, and will enable the use of treatment protocols that are rationally tailored towards each subgroup of the disease
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Methods to verify patient subgroup affiliation will continue to evolve and become increasingly important as subgrouping of patients becomes routine in clinical practice
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Acknowledgements
M. D. Taylor is supported by a Clinician-Scientist Phase II award from the Canadian Institutes of Health Research. Research in the Taylor laboratory is funded by the Pediatric Brain Tumor Foundation and the NIH (R01CA148699). P. A. Northcott is supported by a Roman Herzog Postdoctoral Fellowship. We thank Susan Archer for technical writing assistance.
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P. A. Northcott and M. D. Taylor researched data for the article, provided substantial contributions to discussion of content, wrote the article, and contributed to review and editing of the manuscript before submission. A. Korshunov contributed to writing the article and to the review and editing of the manuscript before submission. S. M. Pfister reviewed and edited the manuscript before submission.
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Northcott, P., Korshunov, A., Pfister, S. et al. The clinical implications of medulloblastoma subgroups. Nat Rev Neurol 8, 340–351 (2012). https://doi.org/10.1038/nrneurol.2012.78
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DOI: https://doi.org/10.1038/nrneurol.2012.78
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