Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

Autor:	Turajlic S; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Renal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Xu H; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Litchfield K; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Rowan A; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Horswell S; Department of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK., Chambers T; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., O'Brien T; Urology Centre, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK., Lopez JI; Department of Pathology, Cruces University Hospital, Biocruces Institute, University of the Basque Country, Barakaldo, Spain., Watkins TBK; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Nicol D; Department of Urology, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Stares M; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Challacombe B; Urology Centre, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK., Hazell S; Department of Pathology, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Chandra A; Department of Pathology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK., Mitchell TJ; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Department of Surgery, Addenbrooke's Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK., Au L; Renal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Eichler-Jonsson C; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Jabbar F; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Soultati A; Department of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK., Chowdhury S; Department of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK., Rudman S; Department of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK., Lynch J; Renal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Fernando A; Urology Centre, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK., Stamp G; Experimental Histopathology Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Nye E; Experimental Histopathology Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Stewart A; Department of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK., Xing W; Department of Scientific Computing, the Francis Crick Institute, London NW1 1AT, UK., Smith JC; Department of Scientific Computing, the Francis Crick Institute, London NW1 1AT, UK., Escudero M; Department of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK., Huffman A; Department of Scientific Computing, the Francis Crick Institute, London NW1 1AT, UK., Matthews N; Advanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK., Elgar G; Advanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK., Phillimore B; Advanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK., Costa M; Advanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK., Begum S; Advanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK., Ward S; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Advanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK., Salm M; Department of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK., Boeing S; Department of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK., Fisher R; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Spain L; Renal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Navas C; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Grönroos E; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Hobor S; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Sharma S; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Aurangzeb I; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Lall S; Department of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK., Polson A; Department of Pathology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK., Varia M; Department of Pathology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK., Horsfield C; Department of Pathology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK., Fotiadis N; Department of Radiology, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Pickering L; Renal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Schwarz RF; Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine, Berlin, Germany., Silva B; Department of Scientific Computing, the Francis Crick Institute, London NW1 1AT, UK., Herrero J; Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London WC1E 6DD, UK., Luscombe NM; Bioinformatics and Computational Biology Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Jamal-Hanjani M; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK., Rosenthal R; Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London WC1E 6DD, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK., Birkbak NJ; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK., Wilson GA; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK., Pipek O; Department of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Hungary., Ribli D; Department of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Hungary., Krzystanek M; Department of Bio and Health Informatics, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Csabai I; Department of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Hungary., Szallasi Z; Department of Bio and Health Informatics, Technical University of Denmark, Kgs Lyngby 2800, Denmark; Computational Health Informatics Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Gore M; Renal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., McGranahan N; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK., Van Loo P; Cancer Genomics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Department of Human Genetics, University of Leuven, 3000 Leuven, Belgium., Campbell P; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK., Larkin J; Renal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK. Electronic address: james.larkin@rmh.nhs.uk., Swanton C; Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK; Department of Medical Oncology, University College London Hospitals, London NW1 2BU, UK. Electronic address: charles.swanton@crick.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2018 Apr 19; Vol. 173 (3), pp. 595-610.e11. Date of Electronic Publication: 2018 Apr 12.
DOI:	10.1016/j.cell.2018.03.043
Abstrakt:	The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance. (Copyright © 2018 Francis Crick Institute. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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