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Timing is everything: A connection between medulloblastoma prognosis and foetal cerebellar development

Lookup NU author(s): Dr Daniel Williamson, Dr Ed Schwalbe, Professor Simon BaileyORCiD, Professor Steven CliffordORCiD


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© 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. The childhood brain tumour medulloblastoma is typically classified into multiple discrete molecular subgroups with characteristic DNA methylation and expression patterns. Several of these subgroups are used as, or proposed to be, an effective basis for treatment stratification. Here, we highlight the close connection between the findings described in a recent series of studies which, together, strongly imply a continuous association between survival outcome, the transcriptional profile of a Group3/Group4 (i.e. non-WNT/non-SHH) medulloblastoma and the specific point during early foetal cerebellar development at which initial pathogenic disruption took place. This has important implications for future efforts to model the disease by incorporating driving molecular features into their specific developmental context. This further suggests that instead of relying upon discrete DNA methylation subgroups, using expression biomarkers as the basis of a continuous risk predictor may produce a more effective risk stratification of patients with Group3/Group4 medulloblastoma.

Publication metadata

Author(s): Williamson D, Schwalbe EC, Bailey S, Clifford SC

Publication type: Review

Publication status: Published

Journal: Neuropathology and Applied Neurobiology

Year: 2023

Volume: 49

Issue: 3

Print publication date: 01/06/2023

Online publication date: 06/04/2023

Acceptance date: 30/03/2023

ISSN (print): 0305-1846

ISSN (electronic): 1365-2990

Publisher: Wiley-Blackwell Publishing Ltd


DOI: 10.1111/nan.12903

PubMed id: 37021628