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The evolutionary dynamics of extrachromosomal DNA in human cancers.
Lange, Joshua T; Rose, John C; Chen, Celine Y; Pichugin, Yuriy; Xie, Liangqi; Tang, Jun; Hung, King L; Yost, Kathryn E; Shi, Quanming; Erb, Marcella L; Rajkumar, Utkrisht; Wu, Sihan; Taschner-Mandl, Sabine; Bernkopf, Marie; Swanton, Charles; Liu, Zhe; Huang, Weini; Chang, Howard Y; Bafna, Vineet; Henssen, Anton G; Werner, Benjamin; Mischel, Paul S.
Afiliação
  • Lange JT; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Rose JC; ChEM-H, Stanford University, Stanford, CA, USA.
  • Chen CY; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Pichugin Y; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Xie L; Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
  • Tang J; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA.
  • Hung KL; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
  • Yost KE; 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.
  • Shi Q; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Erb ML; ChEM-H, Stanford University, Stanford, CA, USA.
  • Rajkumar U; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Wu S; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Taschner-Mandl S; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
  • Bernkopf M; University of California San Diego Light Microscopy Core Facility, Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
  • Swanton C; Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.
  • Liu Z; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Huang W; St. Anna Children's Cancer Research Institute, Vienna, Austria.
  • Chang HY; St. Anna Children's Cancer Research Institute, Vienna, Austria.
  • Bafna V; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Henssen AG; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Werner B; Department of Medical Oncology, University College London Hospitals, London, UK.
  • Mischel PS; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Nat Genet ; 54(10): 1527-1533, 2022 10.
Article em En | MEDLINE | ID: mdl-36123406
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oncogenes / Neoplasias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oncogenes / Neoplasias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos