The evolutionary dynamics of extrachromosomal DNA in human cancers.

Biological Evolution DNA Extrachromosomal Inheritance Humans Neoplasms / genetics Oncogenes

Journal

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

Informations de publication

Date de publication:
10 2022
Historique:
received: 16 02 2022
accepted: 01 08 2022
pubmed: 20 9 2022
medline: 12 10 2022
entrez: 19 9 2022
Statut: ppublish

Résumé

Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Currently, the impact of nonchromosomal oncogene inheritance-random identity by descent-is poorly understood. Also unclear is the impact of ecDNA on somatic variation and selection. Here integrating theoretical models of random segregation, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, we demonstrate that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment. Observed ecDNAs benefit host cell survival or growth and can change within a single cell cycle. ecDNA inheritance can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are facilitated by the ability of ecDNA to rapidly adapt genomes in a way that is not possible through chromosomal oncogene amplification. These results show how the nonchromosomal random inheritance pattern of ecDNA contributes to poor outcomes for patients with cancer.

Identifiants

DOI: 10.1038/s41588-022-01177-x PMID: 36123406 PMC: PMC9534767
pubmed: 36123406
doi: 10.1038/s41588-022-01177-x
pii: 10.1038/s41588-022-01177-x
pmc: PMC9534767
doi:

Substances chimiques

DNA 9007-49-2

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1527-1533

Subventions

Organisme : NCI NIH HHS
ID : R01 CA238249
Pays : United States
Organisme : Cancer Research UK
ID : C11496/A17786
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : F99 CA274692
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA264379
Pays : United States
Organisme : Medical Research Council
ID : FC001169
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001169
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C416/A21999
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM114362
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA209919
Pays : United States
Organisme : Cancer Research UK
ID : C11496/A30025
Pays : United Kingdom
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : OT2 CA278635
Pays : United States
Organisme : Wellcome Trust
ID : FC001169
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Joshua T Lange (JT)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
ChEM-H, Stanford University, Stanford, CA, USA.
ORCID: 0000-0002-4246-6058

John C Rose (JC)

Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
ORCID: 0000-0003-1810-4337

Celine Y Chen (CY)

Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
ORCID: 0000-0002-1579-024X

Yuriy Pichugin (Y)

Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA.

Liangqi Xie (L)

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, California Institute for Regenerative Medicine Center of Excellence, University of California, Berkeley, CA, USA.

Jun Tang (J)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
ChEM-H, Stanford University, Stanford, CA, USA.

King L Hung (KL)

Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
ORCID: 0000-0002-3662-4662

Kathryn E Yost (KE)

Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.

Quanming Shi (Q)

Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.

Marcella L Erb (ML)

University of California San Diego Light Microscopy Core Facility, Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.

Utkrisht Rajkumar (U)

Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.

Sihan Wu (S)

Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
ORCID: 0000-0001-8329-7492

Sabine Taschner-Mandl (S)

St. Anna Children's Cancer Research Institute, Vienna, Austria.
ORCID: 0000-0002-1439-5301

Marie Bernkopf (M)

St. Anna Children's Cancer Research Institute, Vienna, Austria.
ORCID: 0000-0001-6650-4592

Charles Swanton (C)

Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Department of Medical Oncology, University College London Hospitals, London, UK.
ORCID: 0000-0002-4299-3018

Zhe Liu (Z)

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
ORCID: 0000-0002-3592-3150

Weini Huang (W)

Group of Theoretical Biology, The State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-sen University, Guangzhou, China. weini.huang@qmul.ac.uk.
Department of Mathematics, Queen Mary University of London, London, UK. weini.huang@qmul.ac.uk.
ORCID: 0000-0002-9016-2665

Howard Y Chang (HY)

Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA. howchang@stanford.edu.
Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. howchang@stanford.edu.
ORCID: 0000-0002-9459-4393

Vineet Bafna (V)

Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA. vbafna@cs.ucsd.edu.
ORCID: 0000-0002-5810-6241

Anton G Henssen (AG)

Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany.
Berlin Institute of Health, Berlin, Germany.
ORCID: 0000-0003-1534-778X

Benjamin Werner (B)

Evolutionary Dynamics Group, Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.
ORCID: 0000-0002-6857-8699

Paul S Mischel (PS)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. pmischel@stanford.edu.
ChEM-H, Stanford University, Stanford, CA, USA. pmischel@stanford.edu.
ORCID: 0000-0002-4560-2211

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Classifications MeSH

questionsmedicales.fr › Phénomènes biologiques › Évolution biologique › The evolutionary dynamics of extrachromosomal...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › The evolutionary dynamics of extrachromosomal...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité extrachromosomique › The evolutionary dynamics of extrachromosomal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The evolutionary dynamics of extrachromosomal...
questionsmedicales.fr › Tumeurs › The evolutionary dynamics of extrachromosomal...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes tumoraux › Oncogènes › The evolutionary dynamics of extrachromosomal...