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Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal
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 compet...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938365/ https://www.ncbi.nlm.nih.gov/pubmed/29656895 http://dx.doi.org/10.1016/j.cell.2018.03.057 |
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author | Turajlic, Samra Xu, Hang Litchfield, Kevin Rowan, Andrew Chambers, Tim Lopez, Jose I. Nicol, David O’Brien, Tim Larkin, James Horswell, Stuart Stares, Mark Au, Lewis Jamal-Hanjani, Mariam Challacombe, Ben Chandra, Ashish Hazell, Steve Eichler-Jonsson, Claudia Soultati, Aspasia Chowdhury, Simon Rudman, Sarah Lynch, Joanna Fernando, Archana Stamp, Gordon Nye, Emma Jabbar, Faiz Spain, Lavinia Lall, Sharanpreet Guarch, Rosa Falzon, Mary Proctor, Ian Pickering, Lisa Gore, Martin Watkins, Thomas B.K. Ward, Sophia Stewart, Aengus DiNatale, Renzo Becerra, Maria F. Reznik, Ed Hsieh, James J. Richmond, Todd A. Mayhew, George F. Hill, Samantha M. McNally, Catherine D. Jones, Carol Rosenbaum, Heidi Stanislaw, Stacey Burgess, Daniel L. Alexander, Nelson R. Swanton, Charles |
author_facet | Turajlic, Samra Xu, Hang Litchfield, Kevin Rowan, Andrew Chambers, Tim Lopez, Jose I. Nicol, David O’Brien, Tim Larkin, James Horswell, Stuart Stares, Mark Au, Lewis Jamal-Hanjani, Mariam Challacombe, Ben Chandra, Ashish Hazell, Steve Eichler-Jonsson, Claudia Soultati, Aspasia Chowdhury, Simon Rudman, Sarah Lynch, Joanna Fernando, Archana Stamp, Gordon Nye, Emma Jabbar, Faiz Spain, Lavinia Lall, Sharanpreet Guarch, Rosa Falzon, Mary Proctor, Ian Pickering, Lisa Gore, Martin Watkins, Thomas B.K. Ward, Sophia Stewart, Aengus DiNatale, Renzo Becerra, Maria F. Reznik, Ed Hsieh, James J. Richmond, Todd A. Mayhew, George F. Hill, Samantha M. McNally, Catherine D. Jones, Carol Rosenbaum, Heidi Stanislaw, Stacey Burgess, Daniel L. Alexander, Nelson R. Swanton, Charles |
author_sort | Turajlic, Samra |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5938365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-59383652018-05-09 Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal Turajlic, Samra Xu, Hang Litchfield, Kevin Rowan, Andrew Chambers, Tim Lopez, Jose I. Nicol, David O’Brien, Tim Larkin, James Horswell, Stuart Stares, Mark Au, Lewis Jamal-Hanjani, Mariam Challacombe, Ben Chandra, Ashish Hazell, Steve Eichler-Jonsson, Claudia Soultati, Aspasia Chowdhury, Simon Rudman, Sarah Lynch, Joanna Fernando, Archana Stamp, Gordon Nye, Emma Jabbar, Faiz Spain, Lavinia Lall, Sharanpreet Guarch, Rosa Falzon, Mary Proctor, Ian Pickering, Lisa Gore, Martin Watkins, Thomas B.K. Ward, Sophia Stewart, Aengus DiNatale, Renzo Becerra, Maria F. Reznik, Ed Hsieh, James J. Richmond, Todd A. Mayhew, George F. Hill, Samantha M. McNally, Catherine D. Jones, Carol Rosenbaum, Heidi Stanislaw, Stacey Burgess, Daniel L. Alexander, Nelson R. Swanton, Charles Cell Article 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. Cell Press 2018-04-19 /pmc/articles/PMC5938365/ /pubmed/29656895 http://dx.doi.org/10.1016/j.cell.2018.03.057 Text en © 2018 Francis Crick Institute http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Turajlic, Samra Xu, Hang Litchfield, Kevin Rowan, Andrew Chambers, Tim Lopez, Jose I. Nicol, David O’Brien, Tim Larkin, James Horswell, Stuart Stares, Mark Au, Lewis Jamal-Hanjani, Mariam Challacombe, Ben Chandra, Ashish Hazell, Steve Eichler-Jonsson, Claudia Soultati, Aspasia Chowdhury, Simon Rudman, Sarah Lynch, Joanna Fernando, Archana Stamp, Gordon Nye, Emma Jabbar, Faiz Spain, Lavinia Lall, Sharanpreet Guarch, Rosa Falzon, Mary Proctor, Ian Pickering, Lisa Gore, Martin Watkins, Thomas B.K. Ward, Sophia Stewart, Aengus DiNatale, Renzo Becerra, Maria F. Reznik, Ed Hsieh, James J. Richmond, Todd A. Mayhew, George F. Hill, Samantha M. McNally, Catherine D. Jones, Carol Rosenbaum, Heidi Stanislaw, Stacey Burgess, Daniel L. Alexander, Nelson R. Swanton, Charles Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal |
title | Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal |
title_full | Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal |
title_fullStr | Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal |
title_full_unstemmed | Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal |
title_short | Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal |
title_sort | tracking cancer evolution reveals constrained routes to metastases: tracerx renal |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938365/ https://www.ncbi.nlm.nih.gov/pubmed/29656895 http://dx.doi.org/10.1016/j.cell.2018.03.057 |
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