Tracking cancer evolution reveals constrained routes to metastases: TRACERx RenalMore about Open Access at the Crick
Authors listSamra 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 Tom 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
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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.
Issue number 3