%0 Journal Article %A Delaidelli, Alberto %A Burwag, Fares %A Ben-Neriah, Susana %A Suk, Yujin %A Shyp, Taras %A Kosteniuk, Suzanne %A Dunham, Christopher %A Cheng, Sylvia %A Okonechnikov, Konstantin %A Schrimpf, Daniel %A von Deimling, Andreas %A Ellezam, Benjamin %A Perreault, Sébastien %A Singh, Sheila %A Hawkins, Cynthia %A Kool, Marcel %A Pfister, Stefan %A Steidl, Christian %A Hughes, Christopher %A Korshunov, Andrey %A Sorensen, Poul H %T High-resolution proteomic analysis of medulloblastoma clinical samples identifies therapy resistant subgroups and MYC immunohistochemistry as a powerful outcome predictor. %J Neuro-Oncology %V nn %@ 1522-8517 %C Oxford %I Oxford Univ. Press %M DKFZ-2025-00486 %P nn %D 2025 %Z epub %X While international consensus and the 2021 WHO classification recognize multiple molecular medulloblastoma subgroups, these are difficult to identify in clinical practice utilizing routine approaches. As a result, biology-driven risk stratification and therapy assignment for medulloblastoma remains a major clinical challenge. Here, we report mass spectrometry-based analysis of clinical samples for medulloblastoma subgroup discovery, highlighting a MYC-driven prognostic signature and MYC immunohistochemistry (IHC) as a clinically tractable method for improved risk stratification.We analyzed 56 formalin fixed paraffin embedded (FFPE) medulloblastoma samples by data independent acquisition mass spectrometry identifying a MYC proteome signature in therapy resistant Group 3 medulloblastoma. We validated MYC IHC prognostic and predictive value across two Group 3/4 medulloblastoma clinical cohorts (n=362) treated with standard therapies.After exclusion of WNT tumors, MYC IHC was an independent predictor of therapy resistance and death [HRs 23.6 and 3.23; 95 %K FFPE proteomics (Other) %K MYC (Other) %K Medulloblastoma (Other) %K biomarker (Other) %K risk-stratification (Other) %F PUB:(DE-HGF)16 %9 Journal Article %$ pmid:40040502 %R 10.1093/neuonc/noaf046 %U https://inrepo02.dkfz.de/record/299528