TY - JOUR
T1 - The landscape of chromothripsis across adult cancer types
AU - Voronina, Natalia
AU - Wong, John K.L.
AU - Hübschmann, Daniel
AU - Hlevnjak, Mario
AU - Uhrig, Sebastian
AU - Heilig, Christoph E.
AU - Horak, Peter
AU - Kreutzfeldt, Simon
AU - Mock, Andreas
AU - Stenzinger, Albrecht
AU - Hutter, Barbara
AU - Fröhlich, Martina
AU - Brors, Benedikt
AU - Jahn, Arne
AU - Klink, Barbara
AU - Gieldon, Laura
AU - Sieverling, Lina
AU - Feuerbach, Lars
AU - Chudasama, Priya
AU - Beck, Katja
AU - Kroiss, Matthias
AU - Heining, Christoph
AU - Möhrmann, Lino
AU - Fischer, Andrea
AU - Schröck, Evelin
AU - Glimm, Hanno
AU - Zapatka, Marc
AU - Lichter, Peter
AU - Fröhling, Stefan
AU - Ernst, Aurélie
N1 - Funding Information:
We thank the DKFZ Genomics Core facility for excellent support for the sequencing analyses, the DKFZ-Heidelberg Center for Personalized Oncology (DKFZ-HIPO, project number HIPO21) and the Else Kröner Fresenius Foundation, Fritz Thyssen foundation and Wilhelm Sander Foundation for funding.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Chromothripsis is a recently identified mutational phenomenon, by which a presumably single catastrophic event generates extensive genomic rearrangements of one or a few chromosome(s). Considered as an early event in tumour development, this form of genome instability plays a prominent role in tumour onset. Chromothripsis prevalence might have been underestimated when using low-resolution methods, and pan-cancer studies based on sequencing are rare. Here we analyse chromothripsis in 28 tumour types covering all major adult cancers (634 tumours, 316 whole-genome and 318 whole-exome sequences). We show that chromothripsis affects a substantial proportion of human cancers, with a prevalence of 49% across all cases. Chromothripsis generates entity-specific genomic alterations driving tumour development, including clinically relevant druggable fusions. Chromothripsis is linked with specific telomere patterns and univocal mutational signatures in distinct tumour entities. Longitudinal analysis of chromothriptic patterns in 24 matched tumour pairs reveals insights in the clonal evolution of tumours with chromothripsis.
AB - Chromothripsis is a recently identified mutational phenomenon, by which a presumably single catastrophic event generates extensive genomic rearrangements of one or a few chromosome(s). Considered as an early event in tumour development, this form of genome instability plays a prominent role in tumour onset. Chromothripsis prevalence might have been underestimated when using low-resolution methods, and pan-cancer studies based on sequencing are rare. Here we analyse chromothripsis in 28 tumour types covering all major adult cancers (634 tumours, 316 whole-genome and 318 whole-exome sequences). We show that chromothripsis affects a substantial proportion of human cancers, with a prevalence of 49% across all cases. Chromothripsis generates entity-specific genomic alterations driving tumour development, including clinically relevant druggable fusions. Chromothripsis is linked with specific telomere patterns and univocal mutational signatures in distinct tumour entities. Longitudinal analysis of chromothriptic patterns in 24 matched tumour pairs reveals insights in the clonal evolution of tumours with chromothripsis.
UR - http://www.scopus.com/inward/record.url?scp=85084721666&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-16134-7
DO - 10.1038/s41467-020-16134-7
M3 - Article
C2 - 32385320
AN - SCOPUS:85084721666
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2320
ER -