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Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal

Turajlic, S; Xu, H; Litchfield, K; Rowan, A; Horswell, S; Chambers, T; O'Brien, T; ... TRACERx Renal Consortium, .; + view all (2018) Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal. Cell , 173 (3) 595-610.e11. 10.1016/j.cell.2018.03.043. Green open access

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Abstract

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.

Type: Article
Title: Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2018.03.043
Publisher version: https://doi.org/10.1016/j.cell.2018.03.043
Language: English
Additional information: © 2018 Francis Crick Institute. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Branched evolution, cancer evolution, chromosome instability, deterministic evolution, intratumor heterogeneity, linear evolution, metastasis, punctuated evolution, renal cell cancer, tumor diversity
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10047153
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