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Deterministic evolutionary trajectories influence primary tumor growth: TRACERx renal

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Item Type:Article
Title:Deterministic evolutionary trajectories influence primary tumor growth: TRACERx renal
Creators Name:Turajlic, S. and Xu, H. and Litchfield, K. and Rowan, A. and Horswell, S. and Chambers, T. and O'Brien, T. and Lopez, J.I. and Watkins, T.B.K. and Nicol, D. and Stares, M. and Challacombe, B. and Hazell, S. and Chandra, A. and Mitchell, T.J. and Au, L. and Eichler-Jonsson, C. and Jabbar, F. and Soultati, A. and Chowdhury, S. and Rudman, S. and Lynch, J. and Fernando, A. and Stamp, G. and Nye, E. and Stewart, A. and Xing, W. and Smith, J.C. and Escudero, M. and Huffman, A. and Matthews, N. and Elgar, G. and Phillimore, B. and Costa, M. and Begum, S. and Ward, S. and Salm, M. and Boeing, S. and Fisher, R. and Spain, L. and Navas, C. and Grönroos, E. and Hobor, S. and Sharma, S. and Aurangzeb, I. and Lall, S. and Polson, A. and Varia, M. and Horsfield, C. and Fotiadis, N. and Pickering, L. and Schwarz, R.F. and Silva, B. and Herrero, J. and Luscombe, N.M. and Jamal-Hanjani, M. and Rosenthal, R. and Birkbak, N.J. and Wilson, G.A. and Pipek, O. and Ribli, D. and Krzystanek, M. and Csabai, I. and Szallasi, Z. and Gore, M. and McGranahan, N. and Van Loo, P. and Campbell, P. and Larkin, J. and Swanton, C.
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.
Keywords:Renal Cell Cancer, Cancer Evolution, Intratumor Heterogeneity, Metastasis, Tumor Diversity, Deterministic Evolution, Chromosome Instability, Punctuated Evolution, Branched Evolution, Linear Evolution
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:173
Number:3
Page Range:595-610
Date:19 April 2018
Official Publication:https://doi.org/10.1016/j.cell.2018.03.043
PubMed:View item in PubMed

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