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000294669 1001_ $$0P:(DE-He78)16e9e0f392bb4b8756f75b2df29054e4$$aSmirnov, Petr$$b0$$eFirst author$$udkfz
000294669 245__ $$aMulti-omic and single-cell profiling of chromothriptic medulloblastoma reveals genomic and transcriptomic consequences of genome instability.
000294669 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000294669 520__ $$aChromothripsis is a frequent form of genome instability, whereby a presumably single catastrophic event generates extensive genomic rearrangements of one or multiple chromosome(s). However, little is known about the heterogeneity of chromothripsis across different clones from the same tumour, as well as changes in response to treatment. Here we analyse single-cell genomic and transcriptomic alterations linked with chromothripsis in human p53-deficient medulloblastoma and neural stem cells (n = 9). We reconstruct the order of somatic events, identify early alterations likely linked to chromothripsis and depict the contribution of chromothripsis to malignancy. We characterise subclonal variation of chromothripsis and its effects on extrachromosomal circular DNA, cancer drivers and putatively druggable targets. Furthermore, we highlight the causative role and the fitness consequences of specific rearrangements in neural progenitors.
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000294669 650_7 $$2NLM Chemicals$$aTumor Suppressor Protein p53
000294669 650_2 $$2MeSH$$aMedulloblastoma: genetics
000294669 650_2 $$2MeSH$$aMedulloblastoma: pathology
000294669 650_2 $$2MeSH$$aHumans
000294669 650_2 $$2MeSH$$aGenomic Instability
000294669 650_2 $$2MeSH$$aSingle-Cell Analysis: methods
000294669 650_2 $$2MeSH$$aChromothripsis
000294669 650_2 $$2MeSH$$aTranscriptome
000294669 650_2 $$2MeSH$$aCerebellar Neoplasms: genetics
000294669 650_2 $$2MeSH$$aCerebellar Neoplasms: pathology
000294669 650_2 $$2MeSH$$aGenomics: methods
000294669 650_2 $$2MeSH$$aNeural Stem Cells: metabolism
000294669 650_2 $$2MeSH$$aTumor Suppressor Protein p53: genetics
000294669 650_2 $$2MeSH$$aTumor Suppressor Protein p53: metabolism
000294669 650_2 $$2MeSH$$aGene Expression Profiling: methods
000294669 650_2 $$2MeSH$$aMale
000294669 650_2 $$2MeSH$$aFemale
000294669 650_2 $$2MeSH$$aMultiomics
000294669 7001_ $$0P:(DE-He78)2c6d4f81ba6891f170d25801c181ace1$$aPrzybilla, Moritz Jakob$$b1$$eFirst author$$udkfz
000294669 7001_ $$0P:(DE-He78)1fdaffee272e57a73f861a0ea36c4079$$aSimovic-Lorenz, Milena$$b2$$eFirst author$$udkfz
000294669 7001_ $$0P:(DE-He78)498a5d4f8f3df69147c176a184e707f6$$aParra, Rodrigo Gonzalo$$b3$$eFirst author
000294669 7001_ $$0P:(DE-He78)13651c297cb24826d3cc138cef2b54a2$$aSusak, Hana$$b4$$eFirst author
000294669 7001_ $$0P:(DE-He78)e33bb25d8c2a056ddfc1621563fc5c70$$aAichmüller-Ratnaparkhe, Manasi$$b5
000294669 7001_ $$0P:(DE-HGF)0$$aWong, John Kl$$b6
000294669 7001_ $$0P:(DE-He78)467f2d039931bfae1a497c4a6c54804c$$aKörber, Verena$$b7
000294669 7001_ $$0P:(DE-He78)697cb039ca08f3b7e5a2a52dbf020b46$$aMallm, Jan-Philipp$$b8$$udkfz
000294669 7001_ $$0P:(DE-He78)78421a888a27374f1a010a61cde7f6a7$$aPhilippos, George$$b9$$udkfz
000294669 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b10$$udkfz
000294669 7001_ $$0P:(DE-He78)ff4b82323a90d759d3c7eef0fd8ddfe3$$aKolb, Thorsten$$b11$$udkfz
000294669 7001_ $$0P:(DE-He78)c5cc0ee57f0d49302de5365f8cb9206e$$aKumar, Rithu$$b12
000294669 7001_ $$0P:(DE-He78)33cc72e976602ffb5dfcf91f69f97c70$$aCasiraghi, Nicola$$b13$$udkfz
000294669 7001_ $$0P:(DE-He78)34b3639de467b2c700920d7cbc3d2110$$aOkonechnikov, Konstantin$$b14$$udkfz
000294669 7001_ $$00000-0002-3844-9933$$aGhasemi, David R$$b15
000294669 7001_ $$0P:(DE-He78)5100059e746b377e2e0a37c0e24f6bf7$$aMaaß, Kendra Korinna$$b16$$udkfz
000294669 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian$$b17$$udkfz
000294669 7001_ $$aJauch, Anna$$b18
000294669 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b19$$udkfz
000294669 7001_ $$0P:(DE-He78)9dbe272aaadbdc810ab0bb291eae428e$$aHöfer, Thomas$$b20$$udkfz
000294669 7001_ $$0P:(DE-He78)1beba8f953e7ae7e96e8d3e9a48f10f7$$aZapatka, Marc$$b21$$udkfz
000294669 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b22$$udkfz
000294669 7001_ $$00000-0002-0474-2218$$aHuber, Wolfgang$$b23
000294669 7001_ $$0P:(DE-He78)9aabcfee1a1fc9202398a45a63f0b1e3$$aStegle, Oliver$$b24$$eLast author$$udkfz
000294669 7001_ $$0P:(DE-He78)509fb81813c1911954da583129e8ea57$$aErnst, Aurélie$$b25$$eLast author$$udkfz
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