Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review

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  • Author: Turajlic, Samra

    The Francis Crick Institute, United Kingdom

  • Author: Xu, Hang

    The Francis Crick Institute, United Kingdom

  • Author: Litchfield, Kevin

    The Francis Crick Institute, United Kingdom

  • Author: Rowan, Andrew

    The Francis Crick Institute, United Kingdom

  • Author: Horswell, Stuart

    The Francis Crick Institute, United Kingdom

  • Author: Chambers, Tim

    The Francis Crick Institute, United Kingdom

  • Author: O'Brien, Tim

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Lopez, Jose I.

    University of the Basque Country, Spain

  • Author: Watkins, Thomas B K

    The Francis Crick Institute, United Kingdom

  • Author: Nicol, David

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Stares, Mark

    The Francis Crick Institute, United Kingdom

  • Author: Challacombe, Ben

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust

  • Author: Hazell, Steve

    The Royal Marsden National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Chandra, Ashish

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Mitchell, Thomas J.

    Wellcome Sanger Institute, United Kingdom

  • Author: Au, Lewis

    The Royal Marsden National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Eichler-Jonsson, Claudia

    The Francis Crick Institute, United Kingdom

  • Author: Jabbar, Faiz

    The Francis Crick Institute, United Kingdom

  • Author: Soultati, Aspasia

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Chowdhury, Simon

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Rudman, Sarah

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Lynch, Joanna

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Fernando, Archana

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Stamp, Gordon

    The Francis Crick Institute, United Kingdom

  • Author: Nye, Emma

    The Francis Crick Institute, United Kingdom

  • Author: Stewart, Aengus

    The Francis Crick Institute, United Kingdom

  • Author: Xing, Wei

    The Francis Crick Institute, United Kingdom

  • Author: Smith, Jonathan C

    The Francis Crick Institute, United Kingdom

  • Author: Escudero, Mickael

    The Francis Crick Institute, United Kingdom

  • Author: Huffman, Adam

    The Francis Crick Institute, United Kingdom

  • Author: Matthews, Nik

    The Francis Crick Institute, United Kingdom

  • Author: Elgar, Greg

    The Francis Crick Institute, United Kingdom

  • Author: Phillimore, Ben

    The Francis Crick Institute, United Kingdom

  • Author: Costa, Marta

    The Francis Crick Institute, United Kingdom

  • Author: Begum, Sharmin

    The Francis Crick Institute, United Kingdom

  • Author: Ward, Sophia

    The Francis Crick Institute, United Kingdom

  • Author: Salm, Max

    The Francis Crick Institute, United Kingdom

  • Author: Boeing, Stefan

    The Francis Crick Institute, United Kingdom

  • Author: Fisher, Rosalie

    The Francis Crick Institute, United Kingdom

  • Author: Spain, Lavinia

    The Royal Marsden National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Navas, Carolina

    The Francis Crick Institute, United Kingdom

  • Author: Grönroos, Eva

    The Francis Crick Institute, United Kingdom

  • Author: Hobor, Sebastijan

    The Francis Crick Institute, United Kingdom

  • Author: Sharma, Sarkhara

    The Francis Crick Institute, United Kingdom

  • Author: Aurangzeb, Ismaeel

    The Francis Crick Institute, United Kingdom

  • Author: Lall, Sharanpreet

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Polson, Alexander

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Varia, Mary

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Horsfield, Catherine

    Guy’s and St Thomas’ National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Fotiadis, Nicos

    The Royal Marsden National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Pickering, Lisa

    The Royal Marsden National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Schwarz, Roland F

    Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Germany

  • Author: J. V. da Silva, Bruno

    The Francis Crick Institute, United Kingdom

  • Author: Herrero, Javier

    University College London, United Kingdom

  • Author: Luscombe, Nick M

    The Francis Crick Institute, United Kingdom

  • Author: Jamal-Hanjani, Mariam

    University College London, United Kingdom

  • Author: Rosenthal, Rachel

    University College London, United Kingdom

  • Author: Birkbak, Nicolai Juul

    The Francis Crick Institute, United Kingdom

  • Author: Wilson, Gareth A.

    The Francis Crick Institute, United Kingdom

  • Author: Ribli, Dezso

    Eotvos Lorand University, Hungary

  • Author: Pipek, Orsolya

    Eotvos Lorand University, Hungary

  • Author: Krzystanek, Marcin

    Cancer Genomics, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Csabai, István

    Eotvos Lorand University, Hungary

  • Author: Szallasi, Zoltan Imre

    Cancer Genomics, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Gore, Martin

    Royal Marsden NHS Foundation Trust, United Kingdom

  • Author: McGranahan, Nicholas

    University College London, United Kingdom

  • Author: Van Loo, Peter

    The Francis Crick Institute, United Kingdom

  • Author: Campbell, Peter J.

    Wellcome Sanger Institute, United Kingdom

  • Author: Larkin, James

    The Royal Marsden National Health Service (NHS) Foundation Trust, United Kingdom

  • Author: Swanton, Charles

    The Francis Crick Institute, United Kingdom

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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.
Original languageEnglish
Article numbere11
JournalCELL
Volume173
Issue number3
Pages (from-to)595-610
ISSN0092-8674
DOIs
Publication statusPublished - 2018
CitationsWeb of Science® Times Cited: No match on DOI

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