Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases.
Cell. 2018 Apr 12 [Epub]
Samra Turajlic, Hang Xu, Kevin Litchfield, Andrew Rowan, Tim Chambers, Jose I Lopez, David Nicol, Tim O'Brien, James Larkin, Stuart Horswell, Mark Stares, Lewis Au, Mariam Jamal-Hanjani, Ben Challacombe, Ashish Chandra, Steve Hazell, Claudia Eichler-Jonsson, Aspasia Soultati, Simon Chowdhury, Sarah Rudman, Joanna Lynch, Archana Fernando, Gordon Stamp, Emma Nye, Faiz Jabbar, Lavinia Spain, Sharanpreet Lall, Rosa Guarch, Mary Falzon, Ian Proctor, Lisa Pickering, Martin Gore, Thomas B K Watkins, Sophia Ward, Aengus Stewart, Renzo DiNatale, Maria F Becerra, Ed Reznik, James J Hsieh, Todd A Richmond, George F Mayhew, Samantha M Hill, Catherine D McNally, Carol Jones, Heidi Rosenbaum, Stacey Stanislaw, Daniel L Burgess, Nelson R Alexander, Charles Swanton, PEACE , TRACERx Renal Consortium
Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Renal and Skin Units, the Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK., Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Department of Pathology, Cruces University Hospital, Biocruces Institute, University of the Basque Country, Barakaldo, Spain., Department of Urology, the Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK., Urology Centre, Guy's & St Thomas' NHS Foundation Trust, London, UK., Renal and Skin Units, the Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK., Department of Bioinformatics and Biostatistics, 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 Cellular Pathology, Guy's & St Thomas' NHS Foundation Trust, London SE1 7EH, UK., Department of Pathology, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK., Experimental Histopathology Laboratory, the Francis Crick Institute, London NW1 1AT, UK., Department of Pathology, Complejo Hospitalario de Navarra, 31008 Pamplona, Spain., Department of Pathology, University College London Hospitals, London WC1E 6DE, UK., Translational 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., Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University, St. Louis, MO, USA., Roche Sequencing Solutions, Madison, Research & Development, Madison, WI, 53719, USA., Ventana Medical Systems, Tucson, AZ 85755, USA., Translational 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: .