Genomic-transcriptomic evolution in lung cancer and metastasis.

Autor:	Martínez-Ruiz C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Black JRM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Puttick C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Hill MS; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Demeulemeester J; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.; Integrative Cancer Genomics Laboratory, Department of Oncology, KU Leuven, Leuven, Belgium.; VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium., Larose Cadieux E; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.; Medical Genomics, University College London Cancer Institute, London, UK., Thol K; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Jones TP; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; 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., Naceur-Lombardelli C; 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., Prymas P; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Rowan A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Ward S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK.; Advanced Sequencing Facility, The Francis Crick Institute, London, UK., Cubitt L; Advanced Sequencing Facility, The Francis Crick Institute, London, UK., Athanasopoulou F; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK.; Advanced Sequencing Facility, The Francis Crick Institute, London, UK., Pich O; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Karasaki T; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK.; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK., Moore DA; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK.; Department of Cellular Pathology, University College London Hospitals, London, UK., Salgado R; Department of Pathology, ZAS Hospitals, Antwerp, Belgium.; Division of Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Colliver E; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Castignani C; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.; Medical Genomics, University College London Cancer Institute, London, UK., Dietzen M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Huebner A; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Al Bakir M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Tanić M; Medical Genomics, University College London Cancer Institute, London, UK.; Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia., Watkins TBK; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Lim EL; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Al-Rashed AM; Centre for Nephrology, Division of Medicine, University College London, London, UK., Lang D; Scientific Computing STP, Francis Crick Institute, London, UK., Clements J; Scientific Computing STP, Francis Crick Institute, London, UK., Cook DE; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Rosenthal R; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Wilson GA; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., Frankell AM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK., de Carné Trécesson S; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK., East P; Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK., Kanu N; 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.; Tumour Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, London, UK., Birkbak NJ; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK.; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark., Hackshaw A; Cancer Research UK & UCL Cancer Trials Centre, London, UK., Beck S; Medical Genomics, University College London Cancer Institute, London, UK., Van Loo P; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Jamal-Hanjani M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.; Department of Medical Oncology, University College London Hospitals, London, UK., Swanton C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. Charles.Swanton@crick.ac.uk.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute and University College London Cancer Institute, London, UK. Charles.Swanton@crick.ac.uk.; Department of Medical Oncology, University College London Hospitals, London, UK. Charles.Swanton@crick.ac.uk., McGranahan N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. nicholas.mcgranahan.10@ucl.ac.uk.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. nicholas.mcgranahan.10@ucl.ac.uk.
Jazyk:	angličtina
Zdroj:	Nature [Nature] 2023 Apr; Vol. 616 (7957), pp. 543-552. Date of Electronic Publication: 2023 Apr 12.
DOI:	10.1038/s41586-023-05706-4
Abstrakt:	Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy 1 . Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study 2,3 . Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic-transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary-metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis. (© 2023. The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink