ArticleCell2018
Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.
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Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 428 papers.
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428citing papers in PubMed
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Who cites it
428 citing papers in PubMed.
- Do patients with metastatic renal cell carcinoma obtain survival benefits from cytoreductive nephrectomy? A population-based study.Journal of cancer research and clinical oncology · 2023Trial
- Interpretability of radiomics models is improved when using feature group selection strategies for predicting molecular and clinical targets in clear-cell renal cell carcinoma: insights from the TRACERx Renal study.Cancer imaging : the official publication of the International Cancer Imaging Society · 2023Trial
- A Targetable Myeloid Inflammatory State Governs Disease Recurrence in Clear-Cell Renal Cell Carcinoma.Cancer discovery · 2022Trial
- Machine learning uncovers previously undetectable genetic deletions in cancer panel sequencing.NPJ precision oncology · 2026Article
- Proteomic Analysis Identifies Potential Biomarkers of ELOC -Mutated Renal Cell Carcinoma.The American journal of surgical pathology · 2026Article
- Biopsy and identification of risk factors for discordance in renal tumor: results from the BIRD study (UroCCR n°230).World journal of urology · 2026Article
- Molecular underpinnings of metastatic small renal masses.JCI insight · 2026Article
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- Renal cell carcinoma: molecular understanding and therapeutic development.Cell death and differentiation · 2026Review
- Deep visual multi-omics profiling links morphology and molecular programs in clear cell renal cell carcinoma.EMBO molecular medicine · 2026Article
- Review
- Deconvolution of evolutionary architecture unmasks a high-risk, subclonal-rich subtype in treatment-naive small cell lung cancer.Journal of thoracic disease · 2026Article
- Distinct endogenous retroviruses are expressed in mutational subtypes of clear cell renal cell carcinoma and are linked to improved clinical outcomes.Cell reports · 2026Article
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- BAP1 deficiency-induced SKA3 promotes clear cell renal cell carcinoma malignant progression by regulating chromosomal instability.Cell death & disease · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- A single chromosome 3p break initiates clear cell renal cell carcinoma evolution.bioRxiv : the preprint server for biology · 2026Article
- Spatial transcriptomic profiling of ovarian clear cell carcinoma reveals heterogeneity in OXPHOS and EMT gradients.Nature communications · 2026Article
- Kidney-specific HIF-1α-dependent ARL10/miR-1271-5p overexpression in clear cell renal cell carcinoma.British journal of cancer · 2026Article
- Chimeric Antigen Receptor-Immune Cell-Based Therapies for Clear Cell Renal Cell Carcinoma: Latest Advancements and Directions.Cancers · 2026Review
368 more citing papers are in PubMed but not listed here.
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Authors and funding
71 authors.
Samra TurajlicTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Renal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Hang XuTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Kevin LitchfieldTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Andrew RowanTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Stuart HorswellDepartment of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK.
Tim ChambersTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Tim O'BrienUrology Centre, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
Jose I LopezDepartment of Pathology, Cruces University Hospital, Biocruces Institute, University of the Basque Country, Barakaldo, Spain.
Thomas B K WatkinsTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
David NicolDepartment of Urology, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Mark StaresTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Ben ChallacombeUrology Centre, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
Steve HazellDepartment of Pathology, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Ashish ChandraDepartment of Pathology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK.
Thomas J MitchellCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Department of Surgery, Addenbrooke's Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
Lewis AuRenal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Claudia Eichler-JonssonTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Faiz JabbarTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Aspasia SoultatiDepartment of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
Simon ChowdhuryDepartment of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
Sarah RudmanDepartment of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
Joanna LynchRenal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Archana FernandoUrology Centre, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
Gordon StampExperimental Histopathology Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Emma NyeExperimental Histopathology Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Aengus StewartDepartment of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK.
Wei XingDepartment of Scientific Computing, the Francis Crick Institute, London NW1 1AT, UK.
Jonathan C SmithDepartment of Scientific Computing, the Francis Crick Institute, London NW1 1AT, UK.
Mickael EscuderoDepartment of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK.
Adam HuffmanDepartment of Scientific Computing, the Francis Crick Institute, London NW1 1AT, UK.
Nik MatthewsAdvanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK.
Greg ElgarAdvanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK.
Ben PhillimoreAdvanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK.
Marta CostaAdvanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK.
Sharmin BegumAdvanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK.
Sophia WardTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Advanced Sequencing Facility, the Francis Crick Institute, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK.
Max SalmDepartment of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK.
Stefan BoeingDepartment of Bioinformatics and Biostatistics, the Francis Crick Institute, London NW1 1AT, UK.
Rosalie FisherTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Lavinia SpainRenal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Carolina NavasTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Eva GrönroosTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Sebastijan HoborTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Sarkhara SharmaTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Ismaeel AurangzebTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Sharanpreet LallDepartment of Medical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
Alexander PolsonDepartment of Pathology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK.
Mary VariaDepartment of Pathology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK.
Catherine HorsfieldDepartment of Pathology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK.
Nicos FotiadisDepartment of Radiology, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Lisa PickeringRenal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Roland F SchwarzBerlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
Bruno SilvaDepartment of Scientific Computing, the Francis Crick Institute, London NW1 1AT, UK.
Javier HerreroBill Lyons Informatics Centre, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
Nick M LuscombeBioinformatics and Computational Biology Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Mariam Jamal-HanjaniCancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK.
Rachel RosenthalBill Lyons Informatics Centre, UCL Cancer Institute, University College London, London WC1E 6DD, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK.
Nicolai J BirkbakTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK.
Gareth A WilsonTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK.
Orsolya PipekDepartment of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Hungary.
Dezso RibliDepartment of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Hungary.
Marcin KrzystanekDepartment of Bio and Health Informatics, Technical University of Denmark, Kgs Lyngby 2800, Denmark.
Istvan CsabaiDepartment of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Hungary.
Zoltan SzallasiDepartment of Bio and Health Informatics, Technical University of Denmark, Kgs Lyngby 2800, Denmark; Computational Health Informatics Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Martin GoreRenal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Nicholas McGranahanCancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK.
Peter Van LooCancer Genomics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Department of Human Genetics, University of Leuven, 3000 Leuven, Belgium.
Peter CampbellCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
James LarkinRenal and Skin Units, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK. Electronic address: james.larkin@rmh.nhs.uk.
Charles SwantonTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK; Department of Medical Oncology, University College London Hospitals, London NW1 2BU, UK. Electronic address: charles.swanton@crick.ac.uk.
TRACERx Renal Consortium
Funding
Cancer Research UK 17786Cancer Research UK 18176Cancer Research UK 21999Cancer Research UK C50947/A18176Cancer Research UK FC010110Medical Research Council MR/L016311/1Medical Research Council MR/P014712/1Wellcome TrustWellcome Trust 103760/Z/14/ZWellcome Trust WT088340MA
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.
Indexed as
AdultAgedAged, 80 and overAllelesBiomarkers, TumorCarcinoma, Renal CellChromosomesClonal EvolutionDisease ProgressionEvolution, MolecularFemaleGenetic HeterogeneityGenetic VariationHumansKidney NeoplasmsLongitudinal StudiesBiomarkers, Tumorbranched evolutioncancer evolutionchromosome instabilitydeterministic evolutionintratumor heterogeneitylinear evolutionmetastasispunctuated evolutionrenal cell cancertumor diversity
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