Chromothripsis followed by circular recombination drives oncogene amplification in human cancer.

Cell Line, Tumor Chromothripsis Cohort Studies DNA, Circular DNA, Neoplasm Gene Amplification Gene Rearrangement Humans Models, Genetic Mutation Neoplasms / genetics Neuroblastoma / genetics Oncogenes Whole Genome Sequencing

Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
12 2021
Historique:
received: 07 05 2020
accepted: 10 09 2021
pubmed: 17 11 2021
medline: 29 12 2021
entrez: 16 11 2021
Statut: ppublish

Résumé

The mechanisms behind the evolution of complex genomic amplifications in cancer have remained largely unclear. Using whole-genome sequencing data of the pediatric tumor neuroblastoma, we here identified a type of amplification, termed 'seismic amplification', that is characterized by multiple rearrangements and discontinuous copy number levels. Overall, seismic amplifications occurred in 9.9% (274 of 2,756) of cases across 38 cancer types, and were associated with massively increased copy numbers and elevated oncogene expression. Reconstruction of the development of seismic amplification showed a stepwise evolution, starting with a chromothripsis event, followed by formation of circular extrachromosomal DNA that subsequently underwent repetitive rounds of circular recombination. The resulting amplicons persisted as extrachromosomal DNA circles or had reintegrated into the genome in overt tumors. Together, our data indicate that the sequential occurrence of chromothripsis and circular recombination drives oncogene amplification and overexpression in a substantial fraction of human malignancies.

Identifiants

DOI: 10.1038/s41588-021-00951-7 PMID: 34782764
pubmed: 34782764
doi: 10.1038/s41588-021-00951-7
pii: 10.1038/s41588-021-00951-7
doi:

Substances chimiques

DNA, Circular 0
DNA, Neoplasm 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1673-1685

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Carolina Rosswog (C)

Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Else Kröner Forschungskolleg Clonal Evolution in Cancer, University Hospital Cologne, Cologne, Germany.

Christoph Bartenhagen (C)

Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Anne Welte (A)

Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
ORCID: 0000-0002-3695-4856

Yvonne Kahlert (Y)

Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Nadine Hemstedt (N)

Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Witali Lorenz (W)

Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Maria Cartolano (M)

Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Sandra Ackermann (S)

Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
ORCID: 0000-0002-5869-7344

Sven Perner (S)

Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Pathology Research Center Borstel, Leibniz Lung Center, Borstel, Germany.

Wenzel Vogel (W)

Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Pathology Research Center Borstel, Leibniz Lung Center, Borstel, Germany.

Janine Altmüller (J)

Cologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Facility Genomics, Berlin, Germany.
Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.

Peter Nürnberg (P)

Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Cologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Falk Hertwig (F)

Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Gudrun Göhring (G)

Department of Human Genetics, Hannover Medical School (MHH), Hannover, Germany.

Esther Lilienweiss (E)

Department of Internal Medicine, University of Cologne, Cologne, Germany.

Adrian M Stütz (AM)

European Molecular Biology Laboratory Genome Biology Unit, Heidelberg, Germany.

Jan O Korbel (JO)

European Molecular Biology Laboratory Genome Biology Unit, Heidelberg, Germany.
ORCID: 0000-0002-2798-3794

Roman K Thomas (RK)

Department of Translational Genomics, Medical Faculty, University of Cologne, Cologne, Germany.
Department of Pathology, University of Cologne, Cologne, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Martin Peifer (M)

Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. mpeifer@uni-koeln.de.
Department of Translational Genomics, Medical Faculty, University of Cologne, Cologne, Germany. mpeifer@uni-koeln.de.
ORCID: 0000-0002-5243-5503

Matthias Fischer (M)

Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. matthias.fischer@uk-koeln.de.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. matthias.fischer@uk-koeln.de.
ORCID: 0000-0003-1363-1242

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Chromothripsis followed by circular...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Aberrations des chromosomes › Chromothripsis › Chromothripsis followed by circular...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Chromothripsis followed by circular...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Conformation d'acide nucléique › ADN circulaire › Chromothripsis followed by circular...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN tumoral › Chromothripsis followed by circular...
questionsmedicales.fr › Phénomènes génétiques › Mutagenèse › Amplification de gène › Chromothripsis followed by circular...
questionsmedicales.fr › Phénomènes génétiques › Réarrangement des gènes › Chromothripsis followed by circular...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Chromothripsis followed by circular...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles génétiques › Chromothripsis followed by circular...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Chromothripsis followed by circular...
questionsmedicales.fr › Tumeurs › Chromothripsis followed by circular...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Tumeurs neuroectodermiques primitives › Tumeurs neuroectodermiques primitives périphériques › Neuroblastome › Chromothripsis followed by circular...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes tumoraux › Oncogènes › Chromothripsis followed by circular...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Chromothripsis followed by circular...