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The evolution of non-small cell lung cancer metastases in TRACERx.
Al Bakir, Maise; Huebner, Ariana; Martínez-Ruiz, Carlos; Grigoriadis, Kristiana; Watkins, Thomas B K; Pich, Oriol; Moore, David A; Veeriah, Selvaraju; Ward, Sophia; Laycock, Joanne; Johnson, Diana; Rowan, Andrew; Razaq, Maryam; Akther, Mita; Naceur-Lombardelli, Cristina; Prymas, Paulina; Toncheva, Antonia; Hessey, Sonya; Dietzen, Michelle; Colliver, Emma; Frankell, Alexander M; Bunkum, Abigail; Lim, Emilia L; Karasaki, Takahiro; Abbosh, Christopher; Hiley, Crispin T; Hill, Mark S; Cook, Daniel E; Wilson, Gareth A; Salgado, Roberto; Nye, Emma; Stone, Richard Kevin; Fennell, Dean A; Price, Gillian; Kerr, Keith M; Naidu, Babu; Middleton, Gary; Summers, Yvonne; Lindsay, Colin R; Blackhall, Fiona H; Cave, Judith; Blyth, Kevin G; Nair, Arjun; Ahmed, Asia; Taylor, Magali N; Procter, Alexander James; Falzon, Mary; Lawrence, David; Navani, Neal; Thakrar, Ricky M.
Afiliação
  • Al Bakir M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Huebner A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Martínez-Ruiz C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Grigoriadis K; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Watkins TBK; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Pich O; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Moore DA; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Veeriah S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Ward S; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Laycock J; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Johnson D; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Rowan A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Razaq M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Akther M; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Naceur-Lombardelli C; Department of Cellular Pathology, University College London Hospitals, London, UK.
  • Prymas P; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Toncheva A; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Hessey S; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Dietzen M; Advanced Sequencing Facility, The Francis Crick Institute, London, UK.
  • Colliver E; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Frankell AM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Bunkum A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Lim EL; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Karasaki T; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Abbosh C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Hiley CT; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Hill MS; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Cook DE; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Wilson GA; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.
  • Salgado R; Computational Cancer Genomics Research Group, University College London Cancer Institute, London, UK.
  • Nye E; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Stone RK; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Fennell DA; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Price G; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Kerr KM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Naidu B; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Middleton G; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Summers Y; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.
  • Lindsay CR; Computational Cancer Genomics Research Group, University College London Cancer Institute, London, UK.
  • Blackhall FH; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Cave J; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Blyth KG; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Nair A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Ahmed A; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.
  • Taylor MN; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Procter AJ; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Falzon M; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Lawrence D; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Navani N; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Thakrar RM; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Nature ; 616(7957): 534-542, 2023 04.
Article em En | MEDLINE | ID: mdl-37046095
ABSTRACT
Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Clonais / Carcinoma Pulmonar de Células não Pequenas / Evolução Molecular / Evolução Clonal / Neoplasias Pulmonares / Metástase Neoplásica Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Clonais / Carcinoma Pulmonar de Células não Pequenas / Evolução Molecular / Evolução Clonal / Neoplasias Pulmonares / Metástase Neoplásica Idioma: En Ano de publicação: 2023 Tipo de documento: Article