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Pervasive chromosomal instability and karyotype order in tumour evolution.
Watkins, Thomas B K; Lim, Emilia L; Petkovic, Marina; Elizalde, Sergi; Birkbak, Nicolai J; Wilson, Gareth A; Moore, David A; Grönroos, Eva; Rowan, Andrew; Dewhurst, Sally M; Demeulemeester, Jonas; Dentro, Stefan C; Horswell, Stuart; Au, Lewis; Haase, Kerstin; Escudero, Mickael; Rosenthal, Rachel; Bakir, Maise Al; Xu, Hang; Litchfield, Kevin; Lu, Wei Ting; Mourikis, Thanos P; Dietzen, Michelle; Spain, Lavinia; Cresswell, George D; Biswas, Dhruva; Lamy, Philippe; Nordentoft, Iver; Harbst, Katja; Castro-Giner, Francesc; Yates, Lucy R; Caramia, Franco; Jaulin, Fanny; Vicier, Cécile; Tomlinson, Ian P M; Brastianos, Priscilla K; Cho, Raymond J; Bastian, Boris C; Dyrskjøt, Lars; Jönsson, Göran B; Savas, Peter; Loi, Sherene; Campbell, Peter J; Andre, Fabrice; Luscombe, Nicholas M; Steeghs, Neeltje; Tjan-Heijnen, Vivianne C G; Szallasi, Zoltan; Turajlic, Samra; Jamal-Hanjani, Mariam.
Afiliación
  • 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.
  • Petkovic M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Elizalde S; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
  • Birkbak NJ; Department of Mathematics, Dartmouth College, Hanover, NH, USA.
  • Wilson GA; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Moore DA; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.
  • Grönroos E; Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark.
  • Rowan A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Dewhurst SM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Demeulemeester J; Department of Cellular Pathology, University College London Hospitals, London, UK.
  • Dentro SC; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Horswell S; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Au L; Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA.
  • Haase K; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.
  • Escudero M; Department of Human Genetics, University of Leuven, Leuven, Belgium.
  • Rosenthal R; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.
  • Bakir MA; Oxford Big Data Institute, University of Oxford, Oxford, UK.
  • Xu H; Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
  • Litchfield K; Department of Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK.
  • Lu WT; Renal and Skin Units, The Royal Marsden Hospital NHS Foundation Trust, London, UK.
  • Mourikis TP; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK.
  • Dietzen M; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.
  • Spain L; Department of Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK.
  • Cresswell GD; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Biswas D; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Lamy P; Bill Lyons Informatics Centre, University College London Cancer Institute, London, UK.
  • Nordentoft I; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Harbst K; Stanford Cancer Institute, Stanford, CA, USA.
  • Castro-Giner F; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Yates LR; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Caramia F; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Jaulin F; Cancer Genome Evolution Research Group, University College London Cancer Institute, University College London, London, UK.
  • Vicier C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Tomlinson IPM; Cancer Genome Evolution Research Group, University College London Cancer Institute, University College London, London, UK.
  • Brastianos PK; Renal and Skin Units, The Royal Marsden Hospital NHS Foundation Trust, London, UK.
  • Cho RJ; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK.
  • Bastian BC; Bioinformatics and Computational Biology Laboratory, The Francis Crick Institute, London, UK.
  • Dyrskjøt L; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Jönsson GB; Bill Lyons Informatics Centre, University College London Cancer Institute, London, UK.
  • Savas P; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.
  • Loi S; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.
  • Campbell PJ; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.
  • Andre F; Lund University Cancer Centre, Lund University, Lund, Sweden.
  • Luscombe NM; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Steeghs N; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
  • Tjan-Heijnen VCG; Wellcome Trust Sanger Institute, Hinxton, UK.
  • Szallasi Z; Department of Clinical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • Turajlic S; Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.
  • Jamal-Hanjani M; INSERM U1279, Gustave Roussy, Villejuif, France.
Nature ; 587(7832): 126-132, 2020 11.
Article en En | MEDLINE | ID: mdl-32879494
Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes1,2. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution1,3,4. 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Evolución Molecular / Inestabilidad Cromosómica / Cariotipo / Metástasis de la Neoplasia / Neoplasias Límite: Female / Humans / Male Idioma: En Revista: Nature Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Evolución Molecular / Inestabilidad Cromosómica / Cariotipo / Metástasis de la Neoplasia / Neoplasias Límite: Female / Humans / Male Idioma: En Revista: Nature Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido