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Pooling molecular data from a thousand childhood high-grade gliomas showed they are a collection of distinct diseases defined by mutations such as histone H3 K27M and G34R, IDH, and BRAF, with different ages, locations and survival, rather than a single tumour type.
Meta-analysis of published and unpublished molecular data on 1,000 paediatric high-grade gliomas and diffuse intrinsic pontine gliomas, integrating mutations, copy number, methylation and expression to define subgroups by histone H3 and IDH status and by other drivers, with clinical correlates and survival.
Subgroups differed markedly in age, anatomical location and outcome, and the analysis identified targetable alterations (BRAF, NTRK, ALK, ROS1, PDGFRA) in a subset of tumours.
The 2021 WHO paediatric-type diffuse high-grade glioma categories, and the practice of profiling every childhood glioma for a targetable fusion or mutation, rest on this landscape.