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PMID: 29656895 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.

Cell ·Vol. 173 ·No. 3 ·2018-00-19 ·Pages 581-594.e12

Turajlic S, Xu H, Litchfield K, Rowan A, Chambers T, Lopez JI, Nicol D, O'Brien T, Larkin J, Horswell S, Stares M, Au L, Jamal-Hanjani M, Challacombe B, Chandra A, Hazell S, Eichler-Jonsson C, Soultati A, Chowdhury S, Rudman S, Lynch J, Fernando A, Stamp G, Nye E, Jabbar F, Spain L, Lall S, Guarch R, Falzon M, Proctor I, Pickering L, Gore M, Watkins TBK, Ward S, Stewart A, DiNatale R, Becerra MF, Reznik E, Hsieh JJ, Richmond TA, Mayhew GF, Hill SM, McNally CD, Jones C, Rosenbaum H, Stanislaw S, Burgess DL, Alexander NR, Swanton C, PEACE, TRACERx Renal Consortium

Abstract

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.

Keywords
chromosome instability cytoreductive nephrectomy evolution of metastasis loss of 9p metastasectomy metastasis oligometastasis renal cell cancer solitary metastasis
MeSH Terms
Adult Aged Aged, 80 and over Biomarkers/metabolism Biopsy Carcinoma, Renal Cell/genetics,pathology Chromosome Mapping Chromosomes, Human, Pair 14 Chromosomes, Human, Pair 9 Disease Progression Female Humans Kidney Neoplasms/genetics,pathology Longitudinal Studies Male Middle Aged Mutation Neoplasm Metastasis Phenotype Prospective Studies Thrombosis Treatment Outcome
Chemicals
Biomarkers
Authors & Affiliations
51 authors, click to expand affiliations / ORCID
Turajlic Samra
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.
Xu Hang
Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Litchfield Kevin
Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Rowan Andrew
Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Chambers Tim
Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Lopez Jose I
Department of Pathology, Cruces University Hospital, Biocruces Institute, University of the Basque Country, Barakaldo, Spain.
Nicol David
Department of Urology, the Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.
O'Brien Tim
Urology Centre, Guy's & St Thomas' NHS Foundation Trust, London, UK.
Larkin James
Renal and Skin Units, the Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK.
Horswell Stuart
Department of Bioinformatics and Biostatistics, The Francis Crick Institute, London NW1 1AT, UK.
Stares Mark
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.
Au Lewis
Renal and Skin Units, the Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK.
Jamal-Hanjani Mariam
Cancer Research UK Lung Cancer Centre of Excellence London, University College London Cancer Institute, London WC1E 6DD, UK.
Challacombe Ben
Urology Centre, Guy's & St Thomas' NHS Foundation Trust, London, UK.
Chandra Ashish
Department of Cellular Pathology, Guy's & St Thomas' NHS Foundation Trust, London SE1 7EH, UK.
Hazell Steve
Department of Pathology, the Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Eichler-Jonsson Claudia
Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Soultati Aspasia
Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Chowdhury Simon
Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Rudman Sarah
Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Lynch Joanna
Renal and Skin Units, the Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK.
Fernando Archana
Urology Centre, Guy's & St Thomas' NHS Foundation Trust, London, UK.
Stamp Gordon
Experimental Histopathology Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Nye Emma
Experimental Histopathology Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Jabbar Faiz
Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Spain Lavinia
Renal and Skin Units, the Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK.
Lall Sharanpreet
Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Guarch Rosa
Department of Pathology, Complejo Hospitalario de Navarra, 31008 Pamplona, Spain.
Falzon Mary
Department of Pathology, University College London Hospitals, London WC1E 6DE, UK.
Proctor Ian
Department of Pathology, University College London Hospitals, London WC1E 6DE, UK.
Pickering Lisa
Renal and Skin Units, the Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK.
Gore Martin
Renal and Skin Units, the Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK.
Watkins Thomas B K
Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Ward Sophia
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.
Stewart Aengus
Department of Pathology, Cruces University Hospital, Biocruces Institute, University of the Basque Country, Barakaldo, Spain.
DiNatale Renzo
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Becerra Maria F
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Reznik Ed
Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Hsieh James J
Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University, St. Louis, MO, USA.
Richmond Todd A
Roche Sequencing Solutions, Madison, Research & Development, Madison, WI, 53719, USA.
Mayhew George F
Roche Sequencing Solutions, Madison, Research & Development, Madison, WI, 53719, USA.
Hill Samantha M
Ventana Medical Systems, Tucson, AZ 85755, USA.
McNally Catherine D
Ventana Medical Systems, Tucson, AZ 85755, USA.
Jones Carol
Ventana Medical Systems, Tucson, AZ 85755, USA.
Rosenbaum Heidi
Roche Sequencing Solutions, Madison, Research & Development, Madison, WI, 53719, USA.
Stanislaw Stacey
Ventana Medical Systems, Tucson, AZ 85755, USA.
Burgess Daniel L
Roche Sequencing Solutions, Madison, Research & Development, Madison, WI, 53719, USA.
Alexander Nelson R
Ventana Medical Systems, Tucson, AZ 85755, USA.
Swanton Charles
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: charles.swanton@crick.ac.uk.
PEACE
TRACERx Renal Consortium
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2018.03.057
Email
charles.swanton@crick.ac.uk
Published
2018-00-19
Epub
2018-00-12
Pages
581-594.e12
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC5938365
Subset
IM
Grants
Wellcome Trust · FC001202 · United Kingdom
Medical Research Council · MR/L016311/1 · United Kingdom
NCI NIH HHS · P30 CA008748 · United States
Medical Research Council · MR/P014712/1 · United Kingdom
Cancer Research Institute · FC001202 · United States
Cancer Research UK · C50947/A18176 · United Kingdom
Cancer Research UK · FC001202 · United Kingdom
Wellcome Trust · United Kingdom
Databases
ClinicalTrials.gov
NCT03226886, NCT03004755
Corrections
CommentIn
PMID: 29677504
CommentIn
PMID: 29700380
CommentIn
PMID: 29875457
CommentIn
PMID: 29875480
External Links
PubMed source DOI: 10.1016/j.cell.2018.03.057 PMC Full Text View journal details
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