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

Research output: Contribution to journalArticlepeer-review


  • PCAWG Structural Variation Working Group
  • PCAWG Consortium
  • Gianmarco Contino
  • Jose M. C. Tubio

Colleges, School and Institutes

External organisations

  • Biomedical Research Centre (CINBIO), University of Vigo, Vigo, Spain.
  • Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
  • Universidad de Santiago de Compostela
  • Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
  • Department for Human Genetics, Faculty of Medicine, Catholic University of Leuven, Belgium
  • Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Cambridge, UK.
  • Galicia Sur Health Research Institute, Vigo, Spain.
  • Faculty of Science and Technology, University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain.
  • University of Oxford
  • University of Cambridge
  • Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD, USA.
  • Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.
  • Cancer Research UK Cambridge Institute
  • European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, D-69117, Germany.
  • BSC‐CNS Barcelona Supercomputing Center Barcelona Spain
  • Department of Genetics and Informatics Institute, University of Alabama at Birmingham (UAB) School of Medicine, Birmingham, AL, USA.
  • Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Yale University
  • McGill University
  • Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • NIHR Oxford Biomedical Research Centre, Oxford, UK
  • Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD, USA.


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.


Original languageEnglish
Pages (from-to)306-319
Number of pages14
JournalNature Genetics
Issue number3
Early online date5 Feb 2020
Publication statusPublished - Mar 2020


  • Carcinogenesis/genetics, Gene Rearrangement/genetics, Genome, Human/genetics, Humans, Long Interspersed Nucleotide Elements/genetics, Neoplasms/genetics, Retroelements/genetics

ASJC Scopus subject areas