TY  - JOUR
AU  - Smirnov, Petr
AU  - Przybilla, Moritz Jakob
AU  - Simovic-Lorenz, Milena
AU  - Parra, Rodrigo Gonzalo
AU  - Susak, Hana
AU  - Aichmüller-Ratnaparkhe, Manasi
AU  - Wong, John Kl
AU  - Körber, Verena
AU  - Mallm, Jan-Philipp
AU  - Philippos, George
AU  - Sill, Martin
AU  - Kolb, Thorsten
AU  - Kumar, Rithu
AU  - Casiraghi, Nicola
AU  - Okonechnikov, Konstantin
AU  - Ghasemi, David R
AU  - Maaß, Kendra Korinna
AU  - Pajtler, Kristian
AU  - Jauch, Anna
AU  - Korshunov, Andrey
AU  - Höfer, Thomas
AU  - Zapatka, Marc
AU  - Pfister, Stefan
AU  - Huber, Wolfgang
AU  - Stegle, Oliver
AU  - Ernst, Aurélie
TI  - Multi-omic and single-cell profiling of chromothriptic medulloblastoma reveals genomic and transcriptomic consequences of genome instability.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2024-02404
SP  - 10183
PY  - 2024
N1  - #EA:B420#EA:B260#LA:B420#LA:B260#
AB  - 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.
KW  - Medulloblastoma: genetics
KW  - Medulloblastoma: pathology
KW  - Humans
KW  - Genomic Instability
KW  - Single-Cell Analysis: methods
KW  - Chromothripsis
KW  - Transcriptome
KW  - Cerebellar Neoplasms: genetics
KW  - Cerebellar Neoplasms: pathology
KW  - Genomics: methods
KW  - Neural Stem Cells: metabolism
KW  - Tumor Suppressor Protein p53: genetics
KW  - Tumor Suppressor Protein p53: metabolism
KW  - Gene Expression Profiling: methods
KW  - Male
KW  - Female
KW  - Multiomics
KW  - Tumor Suppressor Protein p53 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39580568
DO  - DOI:10.1038/s41467-024-54547-w
UR  - https://inrepo02.dkfz.de/record/294669
ER  -