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. 2023 Jan 11;11:6. doi: 10.1186/s40478-022-01496-4

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© The Author(s) 2023

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 7 — HR-MAS NMR spectroscopy detected fumarate levels group 3 and high LUM gene expression levels in SHH MB patients predict better overall survival. HR-MAS NMR spectroscopy analysis of fumarate in SHH (a, n = 13) and Group 3 (b, n = 16) patients indicates no survival difference for SHH patients (no fumarate detected n = 8; fumarate detected n = 5) but a strong trend for worse overall survival in Group 3 patients (no fumarate detected n = 12; fumarate detected n = 4) with detectable fumarate levels. c Genomic analysis of LUM expression in SHH (c; logrank test, p < 0.001) and Group 3 (d; logrank test, p = 0.056) patients identified that high LUM expression correlates with better overall survival than low LUM expression, whereas the opposite trend is true in Group 3 patients. e A graphical abstract of this study illustrating that by using by using a combination of state-of-the-art techniques (scRNAseq and 3D OrbiSIMS), in a realistic 3D model, we have identified sub-group-specific tumour phenotypes in SHH and Group 3 medulloblastoma. In the SHH sub-group we have demonstrated the formation of an ECM shell-like structure composed of laminin, type I- and VI-collagens and lumican that can be used to identify low-risk SHH tumours. This could facilitate more accurate risk stratification of SHH medulloblastoma. In the Group 3 sub-group we have shown that fumarate accumulation identifies very-high risk patients that could benefit from a chemotherapy combination with NRF2 targeted therapy approaches