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Charles E Massie
Charles E Massie
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Inmaculada Spiteri
Inmaculada Spiteri
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Helen Ross-Adams
Helen Ross-Adams
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Hayley Luxton
Hayley Luxton
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Jonathan Kay
Jonathan Kay
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Hayley C Whitaker
Hayley C Whitaker
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Mark J Dunning
Mark J Dunning
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Alastair D Lamb
Alastair D Lamb
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Antonio Ramos-Montoya
Antonio Ramos-Montoya
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Daniel S Brewer
Daniel S Brewer
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Colin S Cooper
Colin S Cooper
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Rosalind Eeles
Rosalind Eeles
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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UK Prostate ICGC Group
UK Prostate ICGC Group
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Anne Y Warren
Anne Y Warren
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Simon Tavaré
Simon Tavaré
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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David E Neal
David E Neal
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Andy G Lynch
Andy G Lynch
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
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Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multi-focal prostate tumours, we identify promoter methylation of the transcription factor HES5 as an early event in prostate tumourigenesis. We confirm that this epigenetic alteration occurs in 86–97% of cases in two independent prostate cancer cohorts (n=49 and n=39 tumour–normal pairs). Treatment of prostate cancer cells with the demethylating agent 5-aza-2′-deoxycytidine increased HES5 expression and downregulated its transcriptional target HES6, consistent with functional silencing of the HES5 gene in prostate cancer. Finally, we identify and test a transcriptional module involving the AR, ERG, HES1 and HES6 and propose a model for the impact of HES5 silencing on tumourigenesis as a starting point for future functional studies.
