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

Daniel Williamson*, Edward C. Schwalbe, Simon Bailey, Steven C. Clifford

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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 fetal 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.
Original languageEnglish
Article numbere12903
JournalNeuropathology and Applied Neurobiology
Early online date6 Apr 2023
DOIs
Publication statusE-pub ahead of print - 6 Apr 2023

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