ArticleNeuro-oncology2022
Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Outcomes of immunotherapy in medulloblastoma: a systematic review.The oncologist · 2026Pooled it
- Strategic roadmap for delivery of clinical trials in rare childhood central nervous system (CNS) tumours: a multi-stakeholder consensus.British journal of cancer · 2026Article
- Molecular and clinical features of a Japanese medulloblastoma cohort: Subgroup-specific prognostic stratification using economical/accessible diagnostic methods.Brain pathology (Zurich, Switzerland) · 2026Article
- From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- Therapy and biomarker dependent progression-free survival in infant sonic hedgehog medulloblastoma: a multi-national retrospective cohort study.EClinicalMedicine · 2026Article
- MIF-CD74 signaling drives immune modulation in medulloblastoma.Neuro-oncology · 2026Article
- Advancing Medulloblastoma Treatment: Molecular Mechanisms, Drug Repurposing, and Precision Therapies.Molecular diagnosis & therapy · 2026Review
- Single-cell multi-omics identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma.Nature communications · 2025Article
- Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine.Neuropathology : official journal of the Japanese Society of Neuropathology · 2025Article
- High cellular plasticity state of medulloblastoma local recurrence and distant dissemination.Cell reports. Medicine · 2025Article
- Molecular and clinical heterogeneity within MYC-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study.Neuro-oncology · 2025Article
- High-throughput neural stem cell-based drug screening identifies S6K1 inhibition as a selective vulnerability in sonic hedgehog-medulloblastoma.Neuro-oncology · 2024Article
- Mechanistic insights into medulloblastoma relapse.Pharmacology & therapeutics · 2024Review
- Article
- Drivers Underlying Metastasis and Relapse in Medulloblastoma and Targeting Strategies.Cancers · 2024Review
- Brain Tumors: Development, Drug Resistance, and Sensitization - An Epigenetic Approach.Epigenetics · 2023Review
- Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics.Acta neuropathologica · 2023Article
- OpenPBTA: The Open Pediatric Brain Tumor Atlas.Cell genomics · 2023Article
- Clinical, Histological, and Molecular Prognostic Factors in Childhood Medulloblastoma: Where Do We Stand?Diagnostics (Basel, Switzerland) · 2023Review
- Molecular characterisation defines clinically-actionable heterogeneity within Group 4 medulloblastoma and improves disease risk-stratification.Acta neuropathologica · 2023Article
Corrections and comments
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Authors and funding
30 authors at 13 institutions in 7 countries.
Funding
Abstract
backgroundLess than 5% of medulloblastoma (MB) patients survive following failure of contemporary radiation-based therapies. Understanding the molecular drivers of medulloblastoma relapse (rMB) will be essential to improve outcomes. Initial genome-wide investigations have suggested significant genetic divergence of the relapsed disease.
methodsWe undertook large-scale integrated characterization of the molecular features of rMB-molecular subgroup, novel subtypes, copy number variation (CNV), and driver gene mutation. 119 rMBs were assessed in comparison with their paired diagnostic samples (n = 107), alongside an independent reference cohort sampled at diagnosis (n = 282). rMB events were investigated for association with outcome post-relapse in clinically annotated patients (n = 54).
resultsSignificant genetic evolution occurred over disease-course; 40% of putative rMB drivers emerged at relapse and differed significantly between molecular subgroups. Non-infant MBSHH displayed significantly more chromosomal CNVs at relapse (TP53 mutation-associated). Relapsed MBGroup4 demonstrated the greatest genetic divergence, enriched for targetable (eg, CDK amplifications) and novel (eg, USH2A mutations) events. Importantly, many hallmark features of MB were stable over time; novel subtypes (>90% of tumors) and established genetic drivers (eg, SHH/WNT/P53 mutations; 60% of rMB events) were maintained from diagnosis. Critically, acquired and maintained rMB events converged on targetable pathways which were significantly enriched at relapse (eg, DNA damage signaling) and specific events (eg, 3p loss) predicted survival post-relapse.
conclusionsrMB is characterised by the emergence of novel events and pathways, in concert with selective maintenance of established genetic drivers. Together, these define the actionable genetic landscape of rMB and provide a basis for improved clinical management and development of stratified therapeutics, across disease-course.
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