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Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models.
Hynds, Robert E; Huebner, Ariana; Pearce, David R; Hill, Mark S; Akarca, Ayse U; Moore, David A; Ward, Sophia; Gowers, Kate H C; Karasaki, Takahiro; Al Bakir, Maise; Wilson, Gareth A; Pich, Oriol; Martínez-Ruiz, Carlos; Hossain, A S Md Mukarram; Pearce, Simon P; Sivakumar, Monica; Ben Aissa, Assma; Grönroos, Eva; Chandrasekharan, Deepak; Kolluri, Krishna K; Towns, Rebecca; Wang, Kaiwen; Cook, Daniel E; Bosshard-Carter, Leticia; Naceur-Lombardelli, Cristina; Rowan, Andrew J; Veeriah, Selvaraju; Litchfield, Kevin; Crosbie, Philip A J; Dive, Caroline; Quezada, Sergio A; Janes, Sam M; Jamal-Hanjani, Mariam; Marafioti, Teresa; McGranahan, Nicholas; Swanton, Charles.
Affiliation
  • Hynds RE; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. rob.hynds@ucl.ac.uk.
  • Huebner A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. rob.hynds@ucl.ac.uk.
  • Pearce DR; Epithelial Cell Biology in ENT Research Group (EpiCENTR), Developmental Biology and Cancer, Great Ormond Street University College London Institute of Child Health, London, UK. rob.hynds@ucl.ac.uk.
  • Hill MS; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Akarca AU; Cancer Evolution and Genome Instability Laboratory, The Francis Crick 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.
  • Ward S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Gowers KHC; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Karasaki T; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Al Bakir M; Department of Cellular Pathology, University College London Hospitals, London, UK.
  • Wilson GA; 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.
  • Martínez-Ruiz C; Department of Cellular Pathology, University College London Hospitals, London, UK.
  • Hossain ASMM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Pearce SP; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Sivakumar M; Advanced Sequencing Facility, The Francis Crick Institute, London, UK.
  • Ben Aissa A; Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK.
  • Grönroos E; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Chandrasekharan D; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Kolluri KK; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.
  • Towns R; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Wang K; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Cook DE; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Bosshard-Carter L; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Naceur-Lombardelli C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Rowan AJ; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Veeriah S; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Litchfield K; Cancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK.
  • Crosbie PAJ; Cancer Research UK Lung Cancer Centre of Excellence, University of Manchester, Manchester, UK.
  • Dive C; Cancer Research UK National Biomarker Centre, University of Manchester, Manchester, UK.
  • Quezada SA; Cancer Research UK Lung Cancer Centre of Excellence, University of Manchester, Manchester, UK.
  • Janes SM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Jamal-Hanjani M; Department of Cellular Pathology, University College London Hospitals, London, UK.
  • Marafioti T; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
  • McGranahan N; Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK.
  • Swanton C; Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK.
Nat Commun ; 15(1): 4653, 2024 May 31.
Article in En | MEDLINE | ID: mdl-38821942
ABSTRACT
Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Mice, SCID / Mice, Inbred NOD / Carcinoma, Non-Small-Cell Lung / Genetic Heterogeneity / Lung Neoplasms Limits: Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Year: 2024 Document type: Article
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Mice, SCID / Mice, Inbred NOD / Carcinoma, Non-Small-Cell Lung / Genetic Heterogeneity / Lung Neoplasms Limits: Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Year: 2024 Document type: Article