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Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture

Author

Listed:
  • Eva G. Álvarez

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Universidade de Santiago de Compostela)

  • Jonas Demeulemeester

    (The Francis Crick Institute
    University of Leuven)

  • Paula Otero

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Universidade de Santiago de Compostela)

  • Clemency Jolly

    (The Francis Crick Institute)

  • Daniel García-Souto

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Universidade de Santiago de Compostela)

  • Ana Pequeño-Valtierra

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela)

  • Jorge Zamora

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela)

  • Marta Tojo

    (The Biomedical Research Centre (CINBIO), Universidade de Vigo)

  • Javier Temes

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela)

  • Adrian Baez-Ortega

    (University of Cambridge)

  • Bernardo Rodriguez-Martin

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Universidade de Santiago de Compostela)

  • Ana Oitaben

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Universidade de Santiago de Compostela)

  • Alicia L. Bruzos

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Universidade de Santiago de Compostela)

  • Mónica Martínez-Fernández

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela)

  • Kerstin Haase

    (The Francis Crick Institute)

  • Sonia Zumalave

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Universidade de Santiago de Compostela)

  • Rosanna Abal

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela)

  • Jorge Rodríguez-Castro

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela)

  • Aitor Rodriguez-Casanova

    (University Clinical Hospital of Santiago de Compostela (CHUS/SERGAS)
    Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of SantiagodeCompostela(IDIS))

  • Angel Diaz-Lagares

    (University Clinical Hospital of Santiago de Compostela (CHUS/SERGAS)
    Centro de Investigación Biomédica en Red Cáncer (CIBERONC))

  • Yilong Li

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton)

  • Keiran M. Raine

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton)

  • Adam P. Butler

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton)

  • Iago Otero

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Universidade de Santiago de Compostela)

  • Atsushi Ono

    (Graduate School of Biomedical and Health Sciences, Hiroshima University)

  • Hiroshi Aikata

    (Graduate School of Biomedical and Health Sciences, Hiroshima University)

  • Kazuaki Chayama

    (Collaborative Research Laboratory of Medical Innovation, Graduate School of Biomedical and Health Sciences, Hiroshima University
    Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University
    RIKEN Center for Integrative Medical Sciences)

  • Masaki Ueno

    (Wakayama Medical University)

  • Shinya Hayami

    (Wakayama Medical University)

  • Hiroki Yamaue

    (Wakayama Medical University)

  • Kazuhiro Maejima

    (RIKEN Center for Integrative Medical Sciences)

  • Miguel G. Blanco

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela)

  • Xavier Forns

    (Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd)

  • Carmen Rivas

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Centro Nacional de Biotecnología – Consejo Superior de Investigaciones Científicas (CNB – CSIC))

  • Juan Ruiz-Bañobre

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Centro de Investigación Biomédica en Red Cáncer (CIBERONC)
    University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela
    Health Research Institute of Santiago de Compostela (IDIS))

  • Sofía Pérez-del-Pulgar

    (Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd)

  • Raúl Torres-Ruiz

    (Molecular Cytogenetics and Genome Engineering Group, Centro Nacional de Investigaciones Oncológicas (CNIO)
    Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT))

  • Sandra Rodriguez-Perales

    (Molecular Cytogenetics and Genome Engineering Group, Centro Nacional de Investigaciones Oncológicas (CNIO))

  • Urtzi Garaigorta

    (Centro Nacional de Biotecnología – Consejo Superior de Investigaciones Científicas (CNB – CSIC))

  • Peter J. Campbell

    (Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
    University of Cambridge)

  • Hidewaki Nakagawa

    (RIKEN Center for Integrative Medical Sciences)

  • Peter Loo

    (The Francis Crick Institute)

  • Jose M. C. Tubio

    (Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela
    Universidade de Santiago de Compostela)

Abstract

Most cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. Here, using multiplatform sequencing technologies, we identify and characterize a remarkable mutational mechanism in human hepatocellular carcinoma caused by Hepatitis B virus, by which DNA molecules from the virus are inserted into the tumour genome causing dramatic changes in its configuration, including non-homologous chromosomal fusions, dicentric chromosomes and megabase-size telomeric deletions. This aberrant mutational mechanism, present in at least 8% of all HCC tumours, can provide the driver rearrangements that a cancer clone requires to survive and grow, including loss of relevant tumour suppressor genes. Most of these events are clonal and occur early during liver cancer evolution. Real-time timing estimation reveals some HBV-mediated rearrangements occur as early as two decades before cancer diagnosis. Overall, these data underscore the importance of characterising liver cancer genomes for patterns of HBV integration.

Suggested Citation

  • Eva G. Álvarez & Jonas Demeulemeester & Paula Otero & Clemency Jolly & Daniel García-Souto & Ana Pequeño-Valtierra & Jorge Zamora & Marta Tojo & Javier Temes & Adrian Baez-Ortega & Bernardo Rodriguez-, 2021. "Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26805-8
    DOI: 10.1038/s41467-021-26805-8
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    References listed on IDEAS

    as
    1. Yilong Li & Claire Schwab & Sarra L. Ryan & Elli Papaemmanuil & Hazel M. Robinson & Patricia Jacobs & Anthony V. Moorman & Sara Dyer & Julian Borrow & Mike Griffiths & Nyla A. Heerema & Andrew J. Carr, 2014. "Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia," Nature, Nature, vol. 508(7494), pages 98-102, April.
    2. Yilong Li & Nicola D. Roberts & Jeremiah A. Wala & Ofer Shapira & Steven E. Schumacher & Kiran Kumar & Ekta Khurana & Sebastian Waszak & Jan O. Korbel & James E. Haber & Marcin Imielinski & Joachim We, 2020. "Patterns of somatic structural variation in human cancer genomes," Nature, Nature, vol. 578(7793), pages 112-121, February.
    3. Michael R. Stratton & Peter J. Campbell & P. Andrew Futreal, 2009. "The cancer genome," Nature, Nature, vol. 458(7239), pages 719-724, April.
    Full references (including those not matched with items on IDEAS)

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