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Multi-omic and single-cell profiling of chromothriptic medulloblastoma reveals genomic and transcriptomic consequences of genome instability

Chromothripsis 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 wel...

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Hauptverfasser: Smirnov, Petr (VerfasserIn) , Przybilla, Moritz Jakob (VerfasserIn) , Simovic-Lorenz, Milena (VerfasserIn) , Gonzalo Parra, Rodrigo (VerfasserIn) , Susak, Hana (VerfasserIn) , Ratnaparkhe, Manasi (VerfasserIn) , Wong, John K. L. (VerfasserIn) , Körber, Verena (VerfasserIn) , Mallm, Jan-Philipp (VerfasserIn) , Philippos, George (VerfasserIn) , Sill, Martin (VerfasserIn) , Kolb, Thorsten (VerfasserIn) , Kumar, Rithu (VerfasserIn) , Casiraghi, Nicola (VerfasserIn) , Okonechnikov, Konstantin (VerfasserIn) , Ghasemi, David R. (VerfasserIn) , Maaß, Kendra K. (VerfasserIn) , Pajtler, Kristian Wilfried (VerfasserIn) , Jauch, Anna (VerfasserIn) , Korshunov, Andrey (VerfasserIn) , Höfer, Thomas (VerfasserIn) , Zapatka, Marc (VerfasserIn) , Pfister, Stefan (VerfasserIn) , Huber, Wolfgang (VerfasserIn) , Stegle, Oliver (VerfasserIn) , Ernst, Aurélie (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 23 November 2024
In: Nature Communications
Year: 2024, Jahrgang: 15, Pages: 1-20
ISSN:2041-1723
DOI:10.1038/s41467-024-54547-w
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-024-54547-w
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-024-54547-w
Volltext
Verfasserangaben:Petr Smirnov, Moritz J. Przybilla, Milena Simovic-Lorenz, R. Gonzalo Parra, Hana Susak, Manasi Ratnaparkhe, John K.L. Wong, Verena Körber, Jan-Philipp Mallm, George Philippos, Martin Sill, Thorsten Kolb, Rithu Kumar, Nicola Casiraghi, Konstantin Okonechnikov, David R. Ghasemi, Kendra Korinna Maaß, Kristian W. Pajtler, Anna Jauch, Andrey Korshunov, Thomas Höfer, Marc Zapatka, Stefan M. Pfister, Wolfgang Huber, Oliver Stegle, and Aurélie Ernst
Beschreibung
Zusammenfassung:Chromothripsis 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.
Beschreibung:Gesehen am 26.09.2025
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-024-54547-w

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