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Tracking cancer evolution reveals constrained routes to metastases: TRACERx Renal

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journal contribution
posted on 15.10.2020 by 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 BK 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
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.

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