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Evolutionary characterization of lung adenocarcinoma morphology in TRACERx.
Karasaki, Takahiro; Moore, David A; Veeriah, Selvaraju; Naceur-Lombardelli, Cristina; Toncheva, Antonia; Magno, Neil; Ward, Sophia; Bakir, Maise Al; Watkins, Thomas B K; Grigoriadis, Kristiana; Huebner, Ariana; Hill, Mark S; Frankell, Alexander M; Abbosh, Christopher; Puttick, Clare; Zhai, Haoran; Gimeno-Valiente, Francisco; Saghafinia, Sadegh; Kanu, Nnennaya; Dietzen, Michelle; Pich, Oriol; Lim, Emilia L; Martínez-Ruiz, Carlos; Black, James R M; Biswas, Dhruva; Campbell, Brittany B; Lee, Claudia; Colliver, Emma; Enfield, Katey S S; Hessey, Sonya; Hiley, Crispin T; Zaccaria, Simone; Litchfield, Kevin; Birkbak, Nicolai J; Cadieux, Elizabeth Larose; Demeulemeester, Jonas; Van Loo, Peter; Adusumilli, Prasad S; Tan, Kay See; Cheema, Waseem; Sanchez-Vega, Francisco; Jones, David R; Rekhtman, Natasha; Travis, William D; Hackshaw, Allan; Marafioti, Teresa; Salgado, Roberto; Le Quesne, John; Nicholson, Andrew G; McGranahan, Nicholas.
Afiliación
  • Karasaki T; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Moore DA; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Veeriah S; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.
  • Naceur-Lombardelli C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Toncheva A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Magno N; Department of Cellular Pathology, University College London Hospitals, London, UK.
  • Ward S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Bakir MA; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Watkins TBK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Grigoriadis K; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Huebner A; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Hill MS; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Frankell AM; Advanced Sequencing Facility, The Francis Crick Institute, London, UK.
  • Abbosh C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Puttick C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Zhai H; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Gimeno-Valiente F; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Saghafinia S; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Kanu N; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Dietzen M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Pich O; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Lim EL; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Martínez-Ruiz C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Black JRM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Biswas D; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Campbell BB; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Lee C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Colliver E; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Enfield KSS; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Hessey S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Hiley CT; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Zaccaria S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Litchfield K; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Birkbak NJ; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Cadieux EL; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Demeulemeester J; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Van Loo P; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Adusumilli PS; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Tan KS; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Cheema W; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Sanchez-Vega F; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Jones DR; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Rekhtman N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Travis WD; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Hackshaw A; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Marafioti T; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Salgado R; Bill Lyons Informatics Centre, University College London Cancer Institute, London, UK.
  • Le Quesne J; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Nicholson AG; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • McGranahan N; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Nat Med ; 29(4): 833-845, 2023 04.
Article en En | MEDLINE | ID: mdl-37045996
ABSTRACT
Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and 'tumor spread through air spaces' were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Adenocarcinoma / Adenocarcinoma del Pulmón / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Adenocarcinoma / Adenocarcinoma del Pulmón / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido