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Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal

Turajlic, S; Xu, H; Litchfield, K; Rowan, A; Chambers, T; Lopez, JI; Nicol, D; ... Swanton, C; + view all (2018) Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal. Cell , 173 (3) 581-594.e12. 10.1016/j.cell.2018.03.057. Green open access

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Abstract

Summary 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.

Type: Article
Title: Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2018.03.057
Publisher version: https://doi.org/10.1016/j.cell.2018.03.057
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, CELL CARCINOMA, BREAST-CANCER, PANCREATIC-CANCER, TUMOR THROMBUS, CYTOREDUCTIVE NEPHRECTOMY, BRANCHED EVOLUTION, NATURAL-HISTORY, PROSTATE-CANCER, SEQUENCING DATA, EXPRESSION
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10050913
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