ArticleNeuro-oncology2025
High-resolution proteomic analysis of medulloblastoma clinical samples identifies therapy-resistant subgroups and MYC immunohistochemistry as a powerful outcome predictor.
Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Biomarkers of Treatment Response in Paediatric Medulloblastoma.Diagnostics (Basel, Switzerland) · 2026Review
- The value of cerebrospinal fluid cytology in the diagnosis of atypical medulloblastoma: a case report and review of the literature.Frontiers in medicine · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
21 authors.
Funding
Abstract
backgroundWhile 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.
methodsWe 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 2 groups of 3/4 medulloblastoma clinical cohorts (n = 362) treated with standard therapies.
resultsAfter the exclusion of WNT tumors, MYC IHC was an independent predictor of therapy resistance and death [HRs 23.6 and 3.23; 95% confidence interval (CI) 1.04-536.18 and 1.84-5.66; P = .047 and <.001]. Notably, only ~50% of the MYC IHC-positive tumors harbored MYC amplification. Accordingly, cross-validated survival models incorporating MYC IHC outperformed current risk stratification schemes including MYC amplification, and reclassified ~20% of patients into a more appropriate very high-risk category.
conclusionsThis study provides a high-resolution proteomic dataset that can be used as a reference for future biomarker discovery. Biology-driven clinical trials should consider MYC IHC status in their design. Integration of MYC IHC in classification algorithms for non-WNT tumors could be rapidly adopted on a global scale, independently of advanced but technically challenging molecular profiling techniques.
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