Tracking cancer evolution reveals constrained routes to metastases: TRACERx Renal
journal contributionposted on 2020-10-15, 16:01 authored 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.
chromosome instabilitycytoreductive nephrectomyevolution of metastasisloss of 9pmetastasectomymetastasisoligometastasisrenal cell cancersolitary metastasisAdultAgedAged, 80 and overBiomarkersBiopsyCarcinoma, Renal CellChromosome MappingChromosomes, Human, Pair 14Chromosomes, Human, Pair 9Disease ProgressionFemaleHumansKidney NeoplasmsLongitudinal StudiesMaleMiddle AgedMutationNeoplasm MetastasisPhenotypeProspective StudiesThrombosisTreatment OutcomePEACETRACERx Renal ConsortiumSwanton FC001169CBHPRI-ackAS-ackSC-ackTurajlic FC001988Developmental Biology06 Biological Sciences11 Medical and Health Sciences