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@ARTICLE{Smirnov:294669,
author = {P. Smirnov$^*$ and M. J. Przybilla$^*$ and M.
Simovic-Lorenz$^*$ and R. G. Parra$^*$ and H. Susak$^*$ and
M. Aichmüller-Ratnaparkhe$^*$ and J. K. Wong$^*$ and V.
Körber$^*$ and J.-P. Mallm$^*$ and G. Philippos$^*$ and M.
Sill$^*$ and T. Kolb$^*$ and R. Kumar$^*$ and N.
Casiraghi$^*$ and K. Okonechnikov$^*$ and D. R. Ghasemi$^*$
and K. K. Maaß$^*$ and K. Pajtler$^*$ and A. Jauch and A.
Korshunov$^*$ and T. Höfer$^*$ and M. Zapatka$^*$ and S.
Pfister$^*$ and W. Huber and O. Stegle$^*$ and A. Ernst$^*$},
title = {{M}ulti-omic and single-cell profiling of chromothriptic
medulloblastoma reveals genomic and transcriptomic
consequences of genome instability.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2024-02404},
pages = {10183},
year = {2024},
note = {#EA:B420#EA:B260#LA:B420#LA:B260#},
abstract = {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.},
keywords = {Medulloblastoma: genetics / Medulloblastoma: pathology /
Humans / Genomic Instability / Single-Cell Analysis: methods
/ Chromothripsis / Transcriptome / Cerebellar Neoplasms:
genetics / Cerebellar Neoplasms: pathology / Genomics:
methods / Neural Stem Cells: metabolism / Tumor Suppressor
Protein p53: genetics / Tumor Suppressor Protein p53:
metabolism / Gene Expression Profiling: methods / Male /
Female / Multiomics / Tumor Suppressor Protein p53 (NLM
Chemicals)},
cin = {B420 / HD01 / B260 / B060 / B086 / W192 / B062 / B300},
ddc = {500},
cid = {I:(DE-He78)B420-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B260-20160331 / I:(DE-He78)B060-20160331 /
I:(DE-He78)B086-20160331 / I:(DE-He78)W192-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)B300-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39580568},
doi = {10.1038/s41467-024-54547-w},
url = {https://inrepo02.dkfz.de/record/294669},
}