Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.

Autor: Rodriguez-Martin B; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.; Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Alvarez EG; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.; Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Baez-Ortega A; Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK., Zamora J; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; The Biomedical Research Centre (CINBIO), Universidade de Vigo, Vigo, Spain.; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK., Supek F; Genome Data Science, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain., Demeulemeester J; The Francis Crick Institute, London, UK.; Department of Human Genetics, University of Leuven, Leuven, Belgium., Santamarina M; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Ju YS; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.; Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Cambridge, UK., Temes J; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Garcia-Souto D; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Detering H; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.; Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.; Galicia Sur Health Research Institute, Vigo, Spain., Li Y; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK., Rodriguez-Castro J; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Dueso-Barroso A; Faculty of Science and Technology, University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain.; Barcelona Supercomputing Center (BSC), Barcelona, Spain., Bruzos AL; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Dentro SC; The Francis Crick Institute, London, UK.; Experimental Cancer Genetics, Wellcome Sanger Institute, Cambridge, UK.; Oxford Big Data Institute, University of Oxford, Oxford, UK., Blanco MG; DNA Repair and Genome Integrity, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Department of Biochemistry and Molecular Biology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Contino G; Medical Research Council (MRC) Cancer Unit, University of Cambridge, Cambridge, UK., Ardeljan D; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD, USA., Tojo M; The Biomedical Research Centre (CINBIO), Universidade de Vigo, Vigo, Spain.; Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain., Roberts ND; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK., Zumalave S; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Edwards PA; University of Cambridge, Cambridge, UK.; Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Weischenfeldt J; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.; Finsen Laboratory and Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.; Department of Urology, Charité Universitätsmedizin Berlin, Berlin, Germany., Puiggròs M; Barcelona Supercomputing Center (BSC), Barcelona, Spain., Chong Z; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Genetics and Informatics Institute, University of Alabama at Birmingham (UAB) School of Medicine, Birmingham, AL, USA., Chen K; University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lee EA; Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Wala JA; The Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Raine KM; Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Cambridge, UK., Butler A; Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Cambridge, UK., Waszak SM; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany., Navarro FCP; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.; Department of Computer Science, Yale University, New Haven, CT, USA., Schumacher SE; The Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Monlong J; Department of Human Genetics, McGill University, Montreal, Québec, Canada., Maura F; Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Cambridge, UK.; Department of Oncology and Onco-Hematology, University of Milan, Milan, Italy.; Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Bolli N; Department of Oncology and Onco-Hematology, University of Milan, Milan, Italy.; Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Bourque G; Canadian Center for Computational Genomics, McGill University, Montreal, Quebec, Canada., Gerstein M; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.; Department of Computer Science, Yale University, New Haven, CT, USA., Park PJ; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Ludwig Center at Harvard, Boston, MA, USA., Wedge DC; Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Cambridge, UK.; Experimental Cancer Genetics, Wellcome Sanger Institute, Cambridge, UK.; Oxford NIHR Biomedical Research Centre, Oxford, UK., Beroukhim R; The Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Torrents D; Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.; Barcelona Supercomputing Center (BSC), Barcelona, Spain., Korbel JO; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK., Martincorena I; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK., Fitzgerald RC; Medical Research Council (MRC) Cancer Unit, University of Cambridge, Cambridge, UK., Van Loo P; The Francis Crick Institute, London, UK.; Department of Human Genetics, University of Leuven, Leuven, Belgium., Kazazian HH; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD, USA., Burns KH; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD, USA.; McKusick-Nathans Institute of Genetic Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA., Campbell PJ; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK. pc8@sanger.ac.uk.; Department of Haematology, University of Cambridge, Cambridge, UK. pc8@sanger.ac.uk., Tubio JMC; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain. jose.mc.tubio@usc.es.; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain. jose.mc.tubio@usc.es.; Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain. jose.mc.tubio@usc.es.; Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Cambridge, UK. jose.mc.tubio@usc.es.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2020 Mar; Vol. 52 (3), pp. 306-319. Date of Electronic Publication: 2020 Feb 05.
DOI: 10.1038/s41588-019-0562-0
Abstrakt: About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.
Databáze: MEDLINE