Pervasive chromosomal instability and karyotype order in tumour evolution.

Autor: Watkins TBK; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Lim EL; 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., Petkovic M; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany., Elizalde S; Department of Mathematics, Dartmouth College, Hanover, NH, USA., Birkbak NJ; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.; Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark., Wilson GA; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Moore DA; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Department of Cellular Pathology, University College London Hospitals, London, UK., Grönroos E; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Rowan A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Dewhurst SM; Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA., Demeulemeester J; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.; Department of Human Genetics, University of Leuven, Leuven, Belgium., Dentro SC; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.; Oxford Big Data Institute, University of Oxford, Oxford, UK.; Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, UK., Horswell S; Department of Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK., Au L; Renal and Skin Units, The Royal Marsden Hospital NHS Foundation Trust, London, UK.; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK., Haase K; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK., Escudero M; Department of Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK., Rosenthal R; 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.; Bill Lyons Informatics Centre, University College London Cancer Institute, London, UK., Bakir MA; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Xu H; Stanford Cancer Institute, Stanford, CA, USA., Litchfield K; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Lu WT; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Mourikis TP; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, University College London Cancer Institute, University College London, London, UK., Dietzen M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, University College London Cancer Institute, University College London, London, UK., Spain L; Renal and Skin Units, The Royal Marsden Hospital NHS Foundation Trust, London, UK.; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK., Cresswell GD; Bioinformatics and Computational Biology Laboratory, The Francis Crick Institute, London, UK., Biswas D; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Bill Lyons Informatics Centre, University College London Cancer Institute, London, UK., Lamy P; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark., Nordentoft I; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark., Harbst K; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.; Lund University Cancer Centre, Lund University, Lund, Sweden., Castro-Giner F; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland., Yates LR; Wellcome Trust Sanger Institute, Hinxton, UK.; Department of Clinical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK., Caramia F; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia., Jaulin F; INSERM U1279, Gustave Roussy, Villejuif, France., Vicier C; Department of Medical Oncology, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France., Tomlinson IPM; Edinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh, UK., Brastianos PK; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA., Cho RJ; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA., Bastian BC; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Dyrskjøt L; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark., Jönsson GB; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.; Lund University Cancer Centre, Lund University, Lund, Sweden., Savas P; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia., Loi S; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia., Campbell PJ; Wellcome Trust Sanger Institute, Hinxton, UK., Andre F; INSERM U981, PRISM Institute, Gustave Roussy, Villejuif, France.; Department of Medical Oncology, Gustave Roussy, Villejuif, France.; Medical School, Université Paris Saclay, Kremlin Bicetre, France., Luscombe NM; Bioinformatics and Computational Biology Laboratory, The Francis Crick Institute, London, UK.; UCL Genetics Institute, Department of Genetics, Evolution & Environment, University College London, London, UK.; Okinawa Institute of Science & Technology, Okinawa, Japan., Steeghs N; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Tjan-Heijnen VCG; Department of Medical Oncology, School of GROW, Maastricht University Medical Center, Maastricht, The Netherlands., Szallasi Z; Danish Cancer Society Research Center, Copenhagen, Denmark.; Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA.; 2nd Department of Pathology, SE-NAP Brain Metastasis Research Group, Semmelweis University, Budapest, Hungary., Turajlic S; Renal and Skin Units, The Royal Marsden Hospital NHS Foundation Trust, London, UK.; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK., Jamal-Hanjani M; 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., Van Loo P; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK., Bakhoum SF; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Schwarz RF; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany. roland.schwarz@mdc-berlin.de.; German Cancer Consortium (DKTK), partner site Berlin, Berlin, Germany. roland.schwarz@mdc-berlin.de.; German Cancer Research Center (DKFZ), Heidelberg, Germany. roland.schwarz@mdc-berlin.de., McGranahan N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. nicholas.mcgranahan.10@ucl.ac.uk.; Cancer Genome Evolution Research Group, University College London Cancer Institute, University College London, London, UK. nicholas.mcgranahan.10@ucl.ac.uk., Swanton C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. charles.swanton@crick.ac.uk.; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. charles.swanton@crick.ac.uk.; Department of Medical Oncology, University College London Hospitals, London, UK. charles.swanton@crick.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2020 Nov; Vol. 587 (7832), pp. 126-132. Date of Electronic Publication: 2020 Sep 02.
DOI: 10.1038/s41586-020-2698-6
Abstrakt: Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes 1,2 . The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution 1,3,4 . Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results in pervasive SCNA heterogeneity. Parallel evolutionary events, which cause disruption in the same genes (such as BCL9, MCL1, ARNT (also known as HIF1B), TERT and MYC) within separate subclones, were present in 37% of tumours. Most recurrent losses probably occurred before whole-genome doubling, that was found as a clonal event in 49% of tumours. However, loss of heterozygosity at the human leukocyte antigen (HLA) locus and loss of chromosome 8p to a single haploid copy recurred at substantial subclonal frequencies, even in tumours with whole-genome doubling, indicating ongoing karyotype remodelling. Focal amplifications that affected chromosomes 1q21 (which encompasses BCL9, MCL1 and ARNT), 5p15.33 (TERT), 11q13.3 (CCND1), 19q12 (CCNE1) and 8q24.1 (MYC) were frequently subclonal yet appeared to be clonal within single samples. Analysis of an independent series of 1,024 metastatic samples revealed that 13 focal SCNAs were enriched in metastatic samples, including gains in chromosome 8q24.1 (encompassing MYC) in clear cell renal cell carcinoma and chromosome 11q13.3 (encompassing CCND1) in HER2 + breast cancer. Chromosomal instability may enable the continuous selection of SCNAs, which are established as ordered events that often occur in parallel, throughout tumour evolution.
Databáze: MEDLINE