Home > Publications database > Spatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse. > print

001     294744
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024 7 _ |a 10.1038/s41467-024-54709-w
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100 1 _ |a Kats, Ilia
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245 _ _ |a Spatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse.
260 _ _ |a [London]
|c 2024
|b Nature Publishing Group UK
336 7 _ |a article
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520 _ _ |a 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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650 _ 7 |a Hedgehog Proteins
|2 NLM Chemicals
650 _ 7 |a SHH protein, human
|2 NLM Chemicals
650 _ 2 |a Medulloblastoma: genetics
|2 MeSH
650 _ 2 |a Medulloblastoma: pathology
|2 MeSH
650 _ 2 |a Medulloblastoma: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Cerebellar Neoplasms: genetics
|2 MeSH
650 _ 2 |a Cerebellar Neoplasms: pathology
|2 MeSH
650 _ 2 |a Cerebellar Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Hedgehog Proteins: metabolism
|2 MeSH
650 _ 2 |a Hedgehog Proteins: genetics
|2 MeSH
650 _ 2 |a Neoplasm Recurrence, Local: genetics
|2 MeSH
650 _ 2 |a Chromothripsis
|2 MeSH
650 _ 2 |a Child
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Child, Preschool
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Neoplastic
|2 MeSH
650 _ 2 |a Cell Proliferation: genetics
|2 MeSH
650 _ 2 |a Gene Expression Profiling
|2 MeSH
650 _ 2 |a Genomic Instability
|2 MeSH
650 _ 2 |a Clone Cells
|2 MeSH
700 1 _ |a Simovic-Lorenz, Milena
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700 1 _ |a Ernst, Aurélie
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773 _ _ |a 10.1038/s41467-024-54709-w
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