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000294744 1001_ $$0P:(DE-He78)0c219dbc36bb1df7df258d866ef48a80$$aKats, Ilia$$b0$$eFirst author$$udkfz
000294744 245__ $$aSpatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse.
000294744 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000294744 520__ $$aPaediatric 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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000294744 650_7 $$2NLM Chemicals$$aHedgehog Proteins
000294744 650_7 $$2NLM Chemicals$$aSHH protein, human
000294744 650_2 $$2MeSH$$aMedulloblastoma: genetics
000294744 650_2 $$2MeSH$$aMedulloblastoma: pathology
000294744 650_2 $$2MeSH$$aMedulloblastoma: metabolism
000294744 650_2 $$2MeSH$$aHumans
000294744 650_2 $$2MeSH$$aCerebellar Neoplasms: genetics
000294744 650_2 $$2MeSH$$aCerebellar Neoplasms: pathology
000294744 650_2 $$2MeSH$$aCerebellar Neoplasms: metabolism
000294744 650_2 $$2MeSH$$aAnimals
000294744 650_2 $$2MeSH$$aTranscriptome
000294744 650_2 $$2MeSH$$aHedgehog Proteins: metabolism
000294744 650_2 $$2MeSH$$aHedgehog Proteins: genetics
000294744 650_2 $$2MeSH$$aNeoplasm Recurrence, Local: genetics
000294744 650_2 $$2MeSH$$aChromothripsis
000294744 650_2 $$2MeSH$$aChild
000294744 650_2 $$2MeSH$$aMice
000294744 650_2 $$2MeSH$$aMale
000294744 650_2 $$2MeSH$$aFemale
000294744 650_2 $$2MeSH$$aChild, Preschool
000294744 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic
000294744 650_2 $$2MeSH$$aCell Proliferation: genetics
000294744 650_2 $$2MeSH$$aGene Expression Profiling
000294744 650_2 $$2MeSH$$aGenomic Instability
000294744 650_2 $$2MeSH$$aClone Cells
000294744 7001_ $$0P:(DE-He78)1fdaffee272e57a73f861a0ea36c4079$$aSimovic-Lorenz, Milena$$b1$$eFirst author$$udkfz
000294744 7001_ $$0P:(DE-He78)a1d9ea75dd03dbe8e7cd31adc141d10d$$aSchreiber, Hannah$$b2$$eFirst author$$udkfz
000294744 7001_ $$0P:(DE-He78)0178c28b2dee9e8a977975ba9ff006e2$$aSant, Pooja$$b3$$udkfz
000294744 7001_ $$0P:(DE-He78)697cb039ca08f3b7e5a2a52dbf020b46$$aMallm, Jan-Philipp$$b4$$udkfz
000294744 7001_ $$aKörber, Verena$$b5
000294744 7001_ $$0P:(DE-He78)081d2e0ef5b433f60cc6d28496070e8a$$aLi, Albert$$b6
000294744 7001_ $$0P:(DE-He78)925278d3679597a2976f88b0b33cbbb8$$aVelmurugan, Pravin$$b7$$udkfz
000294744 7001_ $$0P:(DE-He78)40d033fc1ce702c778d45aaa3d29a2d7$$aHeuer, Sophie$$b8$$udkfz
000294744 7001_ $$0P:(DE-He78)d2be804ffc90ffc2111f75bc2d4a13ed$$aKües, Luisa$$b9$$udkfz
000294744 7001_ $$0P:(DE-He78)83cd6bd6ea17b47e625c371d6415bdea$$aDevens, Frauke$$b10$$udkfz
000294744 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b11$$udkfz
000294744 7001_ $$0P:(DE-He78)f12dec7b80065347181cf69f8233b40d$$aJugold, Manfred$$b12$$udkfz
000294744 7001_ $$0P:(DE-He78)00f2c4d2003902d3abd37481c5268850$$aMoustafa, Mahmoud$$b13$$udkfz
000294744 7001_ $$0P:(DE-He78)360c5bc2b71a849e35aca747c041dda7$$aAbdollahi, Amir$$b14$$udkfz
000294744 7001_ $$0P:(DE-He78)6c294453ee36ad59deddc5494fa6aa4b$$aWinkler, Frank$$b15$$udkfz
000294744 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b16$$udkfz
000294744 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b17$$udkfz
000294744 7001_ $$0P:(DE-He78)9aabcfee1a1fc9202398a45a63f0b1e3$$aStegle, Oliver$$b18$$udkfz
000294744 7001_ $$0P:(DE-He78)509fb81813c1911954da583129e8ea57$$aErnst, Aurélie$$b19$$eLast author$$udkfz
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