ArticleNature communications2024
Spatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Multiomic profiling links L1 retrotransposition to genomic instability and ecDNA in bladder cancer.Nature communications · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Multimodal integration of pathomics and clinical features improves recurrence risk prediction in pediatric medulloblastoma.Pediatric research · 2026Article
- Prognostic biomarkers and Hedgehog pathway activation in early prostate cancer neuroendocrine differentiation via spatial profiling.NPJ precision oncology · 2026Article
- Targeting SRC enhances differentiation and promotes multifaceted cell death mechanisms in recurrent group 3 medulloblastoma.Cell death & disease · 2026Article
- Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Spatially Resolved Profiling of Compartmentalized Muscle and Brain Inflammation.European journal of immunology · 2025Review
- Cancer therapy resistance from a spatial-omics perspective.Clinical and translational medicine · 2025Review
- Neural cell competition sculpting brain from cradle to grave.National science review · 2025Review
- Spatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse.Nature communications · 2024Article
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Authors and funding
20 authors.
Funding
Abstract
Paediatric medulloblastomas with chromothripsis are characterised by high genomic instability and are among the tumours with the worst prognosis. However, the molecular makeup and the determinants of the aggressiveness of chromothriptic medulloblastoma are not well understood. Here, we apply spatial transcriptomics to profile a cohort of 13 chromothriptic and non-chromothriptic medulloblastomas from the same molecular subgroup. Our data reveal a higher extent of spatial intra-tumour heterogeneity in chromothriptic medulloblastomas compared to non-chromothripictic tumours, which is associated with increased proliferation and stemness, but lower immune infiltration and differentiation. Spatial mapping of genetic subclones of the same tumour identify a regionally distinct architecture and clone-specific phenotypic features, with distinct degrees of differentiation, proliferation and immune infiltration between clones. We conduct temporal profiling of 11 samples from patient-derived xenografts from a patient with chromothriptic medulloblastoma, covering the transition from the minimal residual disease stage to treatment-resistant regrown tumours. In chromothriptic medulloblastoma, an ecosystem of cells from multiple genetic clones resist treatment and lead to relapse. Finally, we identify tumour microtubes in chromothriptic medulloblastoma, calling for exploration of cell network communication as a putative target.
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