Journal article
Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal
The Francis Crick Institute1
Cancer Genomics, Department of Bio and Health Informatics, Technical University of Denmark2
Royal Marsden NHS Foundation Trust3
Guy's and St Thomas' NHS Foundation Trust4
University of the Basque Country5
The Royal Marsden National Health Service (NHS) Foundation Trust6
Wellcome Sanger Institute7
Max Delbrück Center for Molecular Medicine in the Helmholtz Association8
University College London9
Eotvos Lorand University10
Department of Bio and Health Informatics, Technical University of Denmark11
...and 1 moreThe 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.
Language: | English |
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Publisher: | Cell Press |
Year: | 2018 |
Pages: | 595-610 |
ISSN: | 10974172 and 00928674 |
Types: | Journal article |
DOI: | 10.1016/j.cell.2018.03.043 |
Adult Aged Aged, 80 and over Alleles Biomarkers, Tumor Carcinoma, Renal Cell Chromosomes Clonal Evolution Disease Progression Evolution, Molecular Female Genetic Heterogeneity Genetic Variation Humans Kidney Neoplasms Longitudinal Studies Male Middle Aged Models, Statistical Mutation Neoplasm Metastasis Phenotype Phylogeny Prognosis Prospective Studies Sequence Analysis, DNA branched evolution cancer evolution chromosome instability deterministic evolution intratumor heterogeneity linear evolution metastasis punctuated evolution renal cell cancer tumor diversity