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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., Xu, H., Litchfield, K., Rowan, A., Horswell, S., Chambers, T., O'Brien, T., Lopez, J.I., Watkins, T.B.K., Nicol, D., Stares, M., Challacombe, B., Hazell, S., Chandra, A., Mitchell, T.J., Au, L., Eichler-Jonsson, C., Jabbar, F., Soultati, A., Chowdhury, S., Rudman, S., Lynch, J., Fernando, A., Stamp, G., Nye, E., Stewart, A., Xing, W., Smith, J.C., Escudero, M., Huffman, A., Matthews, N., Elgar, G., Phillimore, B., Costa, M., Begum, S., Ward, S., Salm, M., Boeing, S., Fisher, R., Spain, L., Navas, C., Grönroos, E., Hobor, S., Sharma, S., Aurangzeb, I., Lall, S., Polson, A., Varia, M., Horsfield, C., Fotiadis, N., Pickering, L., Schwarz, R.F., Silva, B., Herrero, J., Luscombe, N.M., Jamal-Hanjani, M., Rosenthal, R., Birkbak, N.J., Wilson, G.A., Pipek, O., Ribli, D., Krzystanek, M., Csabai, I., Szallasi, Z., Gore, M., McGranahan, N., Van Loo, P., Campbell, P., 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
Publisher:Cell Press
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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