The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Aalternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.
Cell genomics. 2024 Feb 28 [Epub ahead of print]
Dan J Woodcock, Atef Sahli, Ruxandra Teslo, Vinayak Bhandari, Andreas J Gruber, Aleksandra Ziubroniewicz, Gunes Gundem, Yaobo Xu, Adam Butler, Ezequiel Anokian, Bernard J Pope, Chol-Hee Jung, Maxime Tarabichi, Stefan C Dentro, J Henry R Farmery, CRUK ICGC Prostate Group , Peter Van Loo, Anne Y Warren, Vincent Gnanapragasam, Freddie C Hamdy, G Steven Bova, Christopher S Foster, David E Neal, Yong-Jie Lu, Zsofia Kote-Jarai, Michael Fraser, Robert G Bristow, Paul C Boutros, Anthony J Costello, Niall M Corcoran, Christopher M Hovens, Charlie E Massie, Andy G Lynch, Daniel S Brewer, Rosalind A Eeles, Colin S Cooper, David C Wedge
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK; Big Data Institute, University of Oxford, Oxford, UK., Nuffield Department of Medicine, University of Oxford, Oxford, UK; Big Data Institute, University of Oxford, Oxford, UK., Big Data Institute, University of Oxford, Oxford, UK., Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada., Nuffield Department of Medicine, University of Oxford, Oxford, UK; Big Data Institute, University of Oxford, Oxford, UK; Department of Biology, University of Konstanz, Konstanz, Germany., Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Big Data Institute, University of Oxford, Oxford, UK., Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK; Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK., The Institute of Cancer Research, London, UK., Melbourne Bioinformatics, University of Melbourne, Melbourne, VIC, Australia; Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, Australia; Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC, Australia., Melbourne Bioinformatics, University of Melbourne, Melbourne, VIC, Australia., The Francis Crick Institute, London, UK; Institute of Interdisciplinary Research (IRIBHM), Universite Libre de Bruxelles, Brussels, Belgium., Nuffield Department of Medicine, University of Oxford, Oxford, UK; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK; The Francis Crick Institute, London, UK., Statistics and Computational Biology Laboratory, Cancer Research UK Cambridge Institute, Cambridge, UK., The Francis Crick Institute, London, UK; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Cambridge Urology Translational Research and Clinical Trials Office, Addenbrooke's Hospital, Cambridge, UK; Division of Urology, Department of Surgery, University of Cambridge, Cambridge, UK; Department of Urology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Tays Cancer Center, Tampere University Hospital, Tampere, Finland., HCA Laboratories, London, UK., Uro-Oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, UK; Department of Surgical Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK., Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK., Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Division of Cancer Sciences, Faculty of Biology, Health and Medicine, University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK; CRUK Manchester Institute, University of Manchester, Manchester, UK; Manchester Cancer Research Centre, University of Manchester, Manchester, UK., Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Departments of Human Genetics and Urology, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA., Department of Surgery, University of Melbourne, Melbourne, VIC, Australia; Department of Urology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia., Uro-Oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, UK; Early Detection Programme and Urological Malignancies Programme, Cancer Research UK Cambridge Centre, Department of Oncology, University of Cambridge, Cambridge, UK., Statistics and Computational Biology Laboratory, Cancer Research UK Cambridge Institute, Cambridge, UK; School of Medicine/School of Mathematics and Statistics, University of St Andrews, St Andrews, UK., Norwich Medical School, University of East Anglia, Norwich, UK; Earlham Institute, Norwich, UK. Electronic address: ., The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK. Electronic address: ., The Institute of Cancer Research, London, UK; Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address: ., Nuffield Department of Medicine, University of Oxford, Oxford, UK; Big Data Institute, University of Oxford, Oxford, UK; Manchester Cancer Research Centre, University of Manchester, Manchester, UK; Oxford NIHR Biomedical Research Centre, Oxford, UK; Manchester NIHR Biomedical Research Centre, Manchester, UK. Electronic address: .