ArticleCell2018
Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: 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 329 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
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329citing papers in PubMed, 1 pooled it
46.7field-weighted citation impact, top 1% of its field
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Who cites it
329 citing papers in PubMed, 1 synthesis or guideline pooled it, 545 citations in OpenAlex.
- New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Guideline
- A Phase 1b/2 Study of Talazoparib and Axitinib in Patients with Advanced Clear-cell Renal Cell Carcinoma.European urology oncology · 2025Trial
- A Phase 2 Trial of Talazoparib and Avelumab in Genomically Defined Metastatic Kidney Cancer.European urology oncology · 2024Trial
- Novel model of pyroptosis-related molecular signatures for prognosis prediction of clear cell renal cell carcinoma patients.International journal of medical sciences · 2024Trial
- A Targetable Myeloid Inflammatory State Governs Disease Recurrence in Clear-Cell Renal Cell Carcinoma.Cancer discovery · 2022Trial
- High Response Rate and Durability Driven by HLA Genetic Diversity in Patients with Kidney Cancer Treated with Lenvatinib and Pembrolizumab.Molecular cancer research : MCR · 2021Trial
- Chemical Screening Identifies Danofloxacin as a Self-Renewal Agonist of Embryonic Stem Cells through Alleviation of HDAC1-Mediated Deacetylation of Tert and Prdm10.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A guide to understanding tumour evolution through the lens of population genetics.Nature reviews. Cancer · 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
- 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
- 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
- Von Hippel-Lindau disease: pathophysiological and clinical advances.Familial cancer · 2026Review
- Structure-guided optimization of SLC1A1/EAAT3-selective inhibitors targeting renal cancer metabolism.The EMBO journal · 2026Article
- Metastasis-related genomic aberrations and evolutionary trajectory in uveal melanoma.Experimental & molecular medicine · 2026Article
- Contrasting Features of Papillary and Chromophobe Renal Cell Carcinoma Revealed by Whole-Genome Sequencing.Molecular cancer research : MCR · 2026Article
- Article
- Essential genetic mutations impair DNA damage repair and modulate tumor immune microenvironment in ccRCC.MedScience · 2026Review
269 more citing papers are in PubMed but not listed here.
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Authors and funding
48 authors at 16 institutions in 6 countries.
Thomas J MitchellCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Academic Urology Group, Department of Surgery, Addenbrooke's Hospitals NHS Foundation Trust, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.
Samra TurajlicTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK; Renal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
Andrew RowanTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK.
David NicolRenal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
James H R FarmeryCRUK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.
Tim O'BrienGuy's and St Thomas' National Health Service (NHS) Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Inigo MartincorenaCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Patrick TarpeyCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Nicos AngelopoulosCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Lucy R YatesCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Renal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
Adam P ButlerCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Keiran RaineCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Grant D StewartAcademic Urology Group, Department of Surgery, Addenbrooke's Hospitals NHS Foundation Trust, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.
Ben ChallacombeGuy's and St Thomas' National Health Service (NHS) Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Archana FernandoGuy's and St Thomas' National Health Service (NHS) Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Jose I LopezDepartment of Pathology, Cruces University Hospital, Biocruces Institute, University of the Basque Country (UPV/EHU), Barakaldo, Spain.
Steve HazellTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK.
Ashish ChandraGuy's and St Thomas' National Health Service (NHS) Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Simon ChowdhuryGuy's and St Thomas' National Health Service (NHS) Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Sarah RudmanGuy's and St Thomas' National Health Service (NHS) Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Aspasia SoultatiGuy's and St Thomas' National Health Service (NHS) Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Gordon StampExperimental Histopathology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Nicos FotiadisInterventional Radiology Department, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
Lisa PickeringRenal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
Lewis AuRenal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
Lavinia SpainRenal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
Joanna LynchRenal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
Mark StaresRenal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
Jon TeagueCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Francesco MauraCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
David C WedgeBig Data Institute, University of Oxford, Old Road Campus, Oxford OX3 7FZ, UK.
Stuart HorswellBioinformatics and Biostatistics STP, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Tim ChambersTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK.
Kevin LitchfieldTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK.
Hang XuTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK.
Aengus StewartBioinformatics and Biostatistics STP, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Reza ElaidiHôpital Européen Georges Pompidou 20, rue Leblanc, 75908 Paris, France.
Stéphane OudardHôpital Européen Georges Pompidou 20, rue Leblanc, 75908 Paris, France.
Nicholas McGranahanTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK.
Istvan CsabaiDepartment of Physics of Complex Systems, Eotvos Lorand University, Budapest, Hungary.
Martin GoreRenal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
P Andrew FutrealThe University of Texas MD Anderson Cancer Center, Department of Genomic Medicine, Houston, TX 77030, USA.
James LarkinRenal and Skin Units, The Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK.
Andy G LynchCRUK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK; School of Medicine, University of St. Andrews, North Haugh, St. Andrews KY16 9TF, UK.
Zoltan SzallasiCentre for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark; Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology (CHIP@HST), Harvard Medical School, Boston, MA, USA.
Charles SwantonTranslational Cancer Therapeutics Laboratory, the Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK; Department of Medical Oncology, University College London Hospitals, 235 Euston Rd, Fitzrovia, London NW1 2BU, UK. Electronic address: charles.swanton@crick.ac.uk.
Peter J CampbellCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Department of Haematology, University of Cambridge, Cambridge CB2 2XY, UK. Electronic address: pc8@sanger.ac.uk.
TRACERx Renal Consortium
Wellcome Sanger Institute · GBThe Francis Crick Institute · GBNational Health Service · GBRoyal Marsden NHS Foundation Trust · GBGuy's and St Thomas' NHS Foundation Trust · GBAddenbrooke's Hospital · GBUniversity of Cambridge · GBCRUK Lung Cancer Centre of Excellence · GBEötvös Loránd University · HUHarvard University · USHôpital Européen · FRHôpital Européen Georges-Pompidou · FRHospital de Cruces · ESLondon Cancer · GBOpen Data Institute · GBThe University of Texas MD Anderson Cancer Center · US
Funding
Cancer Research UK 18176Cancer Research UK 20406Cancer Research UK 21777Cancer Research UK C14303/A17197Cancer Research UK C50947/A18176Medical Research Council MR/P014712/1Wellcome TrustWellcome Trust WT088340MA
Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the 5' UTR of TERT, targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening. The most common structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. This event occurs in childhood or adolescence, generally as the initiating event that precedes emergence of the tumor's most recent common ancestor by years to decades. Similar genomic changes drive inherited ccRCC. Modeling differences in age incidence between inherited and sporadic cancers suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred. Early development of ccRCC follows well-defined evolutionary trajectories, offering opportunity for early intervention.
Indexed as
Disease ProgressionMutation5' Untranslated RegionsAdultAgedAged, 80 and overCarcinoma, Renal CellChromosomes, Human, Pair 3Chromosomes, Human, Pair 5FemaleGene DosageGenome, HumanHumansKidney NeoplasmsMaleMiddle Aged5' Untranslated RegionsTelomeraseTERT protein, humanVHL protein, humanVon Hippel-Lindau Tumor Suppressor Proteincancer evolutionchromothripsisclear cell renal cell carcinoma
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.