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Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.
Rodriguez-Martin, Bernardo; Alvarez, Eva G; Baez-Ortega, Adrian; Zamora, Jorge; Supek, Fran; Demeulemeester, Jonas; Santamarina, Martin; Ju, Young Seok; Temes, Javier; Garcia-Souto, Daniel; Detering, Harald; Li, Yilong; Rodriguez-Castro, Jorge; Dueso-Barroso, Ana; Bruzos, Alicia L; Dentro, Stefan C; Blanco, Miguel G; Contino, Gianmarco; Ardeljan, Daniel; Tojo, Marta; Roberts, Nicola D; Zumalave, Sonia; Edwards, Paul A; Weischenfeldt, Joachim; Puiggròs, Montserrat; Chong, Zechen; Chen, Ken; Lee, Eunjung Alice; Wala, Jeremiah A; Raine, Keiran M; Butler, Adam; Waszak, Sebastian M; Navarro, Fabio C P; Schumacher, Steven E; Monlong, Jean; Maura, Francesco; Bolli, Niccolo; Bourque, Guillaume; Gerstein, Mark; Park, Peter J; Wedge, David C; Beroukhim, Rameen; Torrents, David; Korbel, Jan O; Martincorena, Iñigo; Fitzgerald, Rebecca C; Van Loo, Peter; Kazazian, Haig H; Burns, Kathleen H; Campbell, Peter J.
Afiliação
  • Rodriguez-Martin B; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Alvarez EG; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.
  • Baez-Ortega A; Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Zamora J; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Supek F; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.
  • Demeulemeester J; Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Santamarina M; Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
  • Ju YS; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Temes J; Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Garcia-Souto D; The Biomedical Research Centre (CINBIO), Universidade de Vigo, Vigo, Spain.
  • Detering H; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
  • Li Y; Genome Data Science, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Rodriguez-Castro J; Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
  • Dueso-Barroso A; The Francis Crick Institute, London, UK.
  • Bruzos AL; Department of Human Genetics, University of Leuven, Leuven, Belgium.
  • Dentro SC; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Blanco MG; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.
  • Contino G; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Ardeljan D; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
  • Tojo M; Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Cambridge, UK.
  • Roberts ND; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Zumalave S; Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Edwards PA; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Weischenfeldt J; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.
  • Puiggròs M; Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.
  • Chong Z; Galicia Sur Health Research Institute, Vigo, Spain.
  • Chen K; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
  • Lee EA; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Wala JA; Faculty of Science and Technology, University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain.
  • Raine KM; Barcelona Supercomputing Center (BSC), Barcelona, Spain.
  • Butler A; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Waszak SM; Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.
  • Navarro FCP; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Schumacher SE; The Francis Crick Institute, London, UK.
  • Monlong J; Experimental Cancer Genetics, Wellcome Sanger Institute, Cambridge, UK.
  • Maura F; Oxford Big Data Institute, University of Oxford, Oxford, UK.
  • Bolli N; DNA Repair and Genome Integrity, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Bourque G; Department of Biochemistry and Molecular Biology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Gerstein M; Medical Research Council (MRC) Cancer Unit, University of Cambridge, Cambridge, UK.
  • Park PJ; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD, USA.
  • Wedge DC; The Biomedical Research Centre (CINBIO), Universidade de Vigo, Vigo, Spain.
  • Beroukhim R; Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.
  • Torrents D; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
  • Korbel JO; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Martincorena I; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Fitzgerald RC; University of Cambridge, Cambridge, UK.
  • Van Loo P; Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Kazazian HH; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
  • Burns KH; Finsen Laboratory and Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
  • Campbell PJ; Barcelona Supercomputing Center (BSC), Barcelona, Spain.
Nat Genet ; 52(3): 306-319, 2020 03.
Article em En | MEDLINE | ID: mdl-32024998
ABSTRACT
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rearranjo Gênico / Genoma Humano / Retroelementos / Elementos Nucleotídeos Longos e Dispersos / Carcinogênese / Neoplasias Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rearranjo Gênico / Genoma Humano / Retroelementos / Elementos Nucleotídeos Longos e Dispersos / Carcinogênese / Neoplasias Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Espanha