ArticleNature genetics2015
Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.
Erratum issuedOpen access · greenAbstract read
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Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 252 papers.
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252citing papers in PubMed
24.7field-weighted citation impact, top 1% of its field
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Who cites it
252 citing papers in PubMed, 454 citations in OpenAlex.
- Phase II Randomized Study of MK-2206 and Bicalutamide in Prostate Cancer Patients With Rising PSA After Primary Therapy (ECOG-ACRIN E2809).The Prostate · 2026Trial
- Neoadjuvant fuzuloparib combined with abiraterone for localized high-risk prostate cancer (FAST-PC): A single-arm phase 2 study.Cell reports. Medicine · 2025Trial
- Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention-results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial.The American journal of clinical nutrition · 2019Trial
- Characterizing population-wide genomic risk distribution for development of a novel clinical-genomic risk system for prognostication in patients with clinically localized prostate cancer.Prostate cancer and prostatic diseases · 2026Article
- Circulating tumour cells as a window into lethality in prostate cancer.Nature reviews. Urology · 2026Review
- Outcomes of Radiotherapy With or Without Dose Escalation to Lymph Node Metastases Detected by PET PSMA or Conventional Imaging in Node-Positive Prostate Cancer: A Real-World Multicenter Propensity Score-Matched (PRIMENOD) Analysis.Clinical nuclear medicine · 2026Article
- Single base focal hypermutation cooccurs with structural variation as an early event in advanced prostate tumourigenesis with ancestry specific independence: a multi-ancestral observational study.Genome medicine · 2026Observational
- Review
- Transient centrosome loss in cultured prostate epithelial cells induces chromosomal instability to produce an oncogenic genotype that correlates with poor clinical outcomes.British journal of cancer · 2026Article
- Clarification of methodology and findings from the NeuroSAFE PROOF randomised controlled trial.Translational andrology and urology · 2026Article
- Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution.International journal of cancer · 2026Review
- Bioinformatics of Shallow Whole Genome Sequencing Data of Circulating Tumor Cells to Inform Cancer Diagnosis and Treatment.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Mechanistic insights and molecular therapy for neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- A head-to-head comparison of sextant-systematic biopsy vs. extended-systematic biopsy for prostate cancer diagnosis in the era of MRI-targeted biopsy: SEXTANT-PRO non-inferiority randomized clinical trial.EClinicalMedicine · 2025Article
- Unravelling the genetics and epigenetics of the ageing tumour microenvironment in cancer.Nature reviews. Cancer · 2025Review
- Single base focal hypermutation cooccurs with structural variation as an early event in advanced prostate tumourigenesis with ancestry specific independence: a multi-ancestral observational study.Research square · 2025Article
- What spatial omics is teaching us about field cancerisation in prostate and bladder cancer.BJU international · 2025Review
- Can Genomic Classifiers in Biopsy Cores With Grade Group 1 Cancer Predict Higher-Grade Disease Elsewhere in the Prostate? Results From the Prospective Miami Active Surveillance Trial.The Journal of urology · 2025Article
- Impact of Surgical Margin Control in Index Tumors on Prognosis After Radical Prostatectomy: A Focus on Zonal Origin.Current oncology (Toronto, Ont.) · 2025Article
- Prostate cancer epigenetics - from pathophysiology to clinical application.Nature reviews. Urology · 2025Review
192 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
72 authors at 11 institutions in 5 countries.
Colin S Cooper *Division of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
Rosalind Eeles *Division of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
David C Wedge *Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Peter Van Loo *Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Gunes GundemCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Ludmil B AlexandrovCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Barbara KremeyerCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Adam ButlerCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Andrew G LynchStatistics and Computational Biology Laboratory, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
Niedzica CamachoDivision of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
Charlie E MassieUrological Research Laboratory, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
Jonathan KayUrological Research Laboratory, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
Hayley J LuxtonUrological Research Laboratory, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
Sandra EdwardsDivision of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
ZSofia Kote-JaraiDivision of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
Nening DennisRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Sue MersonDivision of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
Daniel LeongamornlertDivision of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
Jorge ZamoraCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Cathy CorbishleyDepartment of Histopathology, St Georges Hospital, London, UK.
Sarah ThomasRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Serena Nik-ZainalCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Sarah O'MearaCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Lucy MatthewsDivision of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
Jeremy ClarkNorwich Medical School, University of East Anglia, Norwich, UK.
Rachel HurstNorwich Medical School, University of East Anglia, Norwich, UK.
Richard MithenInstitute of Food Research, Norwich Research Park, Norwich, UK.
Robert G BristowDepartment of Medical Biophysics, University of Toronto, Toronto, Canada.
Paul C BoutrosDepartment of Medical Biophysics, University of Toronto, Toronto, Canada.
Michael FraserDepartment of Radiation Oncology, University of Toronto, Toronto, Canada.
Susanna CookeCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Keiran RaineCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
David JonesCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Andrew MenziesCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Lucy StebbingsCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Jon HintonCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Jon TeagueCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Stuart McLarenCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Laura MudieCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Claire HardyCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Elizabeth AndersonCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Olivia JosephCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Victoria GoodyCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Ben RobinsonCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Mark MaddisonCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Stephen GambleCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Christopher GreenmanSchool of Computing Sciences, University of East Anglia, Norwich, UK.
Dan BerneyDepartment of Molecular Oncology, Barts Cancer Centre, Barts and the London School of Medicine and Dentistry, London, UK.
Steven HazellRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Naomi LivniRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
ICGC Prostate Group
Cyril FisherRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Christopher OgdenRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Pardeep KumarRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Alan ThompsonRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Christopher WoodhouseRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
David NicolRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Erik MayerRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Tim DudderidgeRoyal Marsden NHS Foundation Trust, London and Sutton, UK.
Nimish C ShahUrological Research Laboratory, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
Vincent GnanapragasamUrological Research Laboratory, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
Thierry VoetLaboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
Peter CampbellCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Andrew FutrealCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Douglas EastonCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Anne Y Warren *Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Christopher S Foster *University of Liverpool, Liverpool, UK.
Michael R StrattonCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Hayley C Whitaker *Urological Research Laboratory, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
Ultan McDermott *Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Daniel S Brewer *Division of Genetics and Epidemiology, The Institute Of Cancer Research, London, UK.
David E Neal *Urological Research Laboratory, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
Wellcome Sanger Institute · GBRoyal Marsden NHS Foundation Trust · GBCancer Research UK · GBUniversity of East Anglia · GBInstitute of Cancer Research · GBUniversity of Cambridge · GBSt George's Hospital · GBUniversity of Liverpool · GBUniversity of Toronto · CAOntario Institute for Cancer Research · CAUniversity Health Network · CA
Funding
Cancer Research UK 14835Cancer Research UK 15007Cancer Research UK 17528Cancer Research UK 20406Cancer Research UK A12758Cancer Research UK C5047/A14835Wellcome Trust
Abstract
Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.
Indexed as
DNA Mutational AnalysisCase-Control StudiesCell LineageClonal EvolutionClone CellsHumansMaleMutationNeoplasms, Multiple PrimaryPhylogenyProstateProstatic Neoplasms
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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.