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

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Abstrakt

Tytuł:: Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.
Autorzy:: Álvarez EG; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Demeulemeester J; The Francis Crick Institute, London, NW1 1AT, UK.; Department of Human Genetics, University of Leuven, Leuven, B-3000, Belgium.
Otero P; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Jolly C; The Francis Crick Institute, London, NW1 1AT, UK.
García-Souto D; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Pequeño-Valtierra A; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Zamora J; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Tojo M; The Biomedical Research Centre (CINBIO), Universidade de Vigo, Vigo, 36310, Spain.
Temes J; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Baez-Ortega A; Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES, UK.
Rodriguez-Martin B; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Oitaben A; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Bruzos AL; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Martínez-Fernández M; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Haase K; The Francis Crick Institute, London, NW1 1AT, UK.
Zumalave S; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Abal R; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Rodríguez-Castro J; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Rodriguez-Casanova A; Cancer Epigenomics, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, 15706, Spain.; Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of SantiagodeCompostela(IDIS), Santiago de Compostela, 15706, Spain.
Diaz-Lagares A; Cancer Epigenomics, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, 15706, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, 28029, Spain.
Li Y; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Raine KM; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Butler AP; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Otero I; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Ono A; Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Aikata H; Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Chayama K; Collaborative Research Laboratory of Medical Innovation, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.; Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
Ueno M; Department of Surgery II, Wakayama Medical University, Wakayama, Japan.
Hayami S; Department of Surgery II, Wakayama Medical University, Wakayama, Japan.
Yamaue H; Department of Surgery II, Wakayama Medical University, Wakayama, Japan.
Maejima K; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
Blanco MG; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Forns X; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
Rivas C; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología - Consejo Superior de Investigaciones Científicas (CNB - CSIC), Madrid, 28049, Spain.
Ruiz-Bañobre J; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, 28029, Spain.; Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela, Santiago de Compostela, 15706, Spain.; Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, 15706, Spain.
Pérez-Del-Pulgar S; Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
Torres-Ruiz R; Molecular Cytogenetics and Genome Engineering Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.; Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain.
Rodriguez-Perales S; Molecular Cytogenetics and Genome Engineering Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Garaigorta U; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología - Consejo Superior de Investigaciones Científicas (CNB - CSIC), Madrid, 28049, Spain.
Campbell PJ; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.; Department of Haematology, University of Cambridge, Cambridge, CB2 2XY, UK.
Nakagawa H; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
Van Loo P; The Francis Crick Institute, London, NW1 1AT, UK.
Tubio JMC; Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain. .; Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain. .
Źródło:: Nature communications [Nat Commun] 2021 Nov 25; Vol. 12 (1), pp. 6910. Date of Electronic Publication: 2021 Nov 25.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : Nature Pub. Group
MeSH Terms:: DNA, Viral*
Genome, Human*
Carcinoma, Hepatocellular/*genetics
Hepatitis B virus/*genetics
Liver Neoplasms/*genetics
Carcinoma, Hepatocellular/virology ; Gene Expression Regulation, Neoplastic ; Humans ; Virus Integration ; Whole Genome Sequencing
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Grant Information:: United Kingdom WT_ Wellcome Trust; FC001202 United Kingdom ARC_ Arthritis Research UK; MR/L016311/1 United Kingdom MRC_ Medical Research Council
Substance Nomenclature:: 0 (DNA, Viral)
Entry Date(s):: Date Created: 20211126 Date Completed: 20220103 Latest Revision: 20230208
Update Code:: 20240104
PubMed Central ID:: PMC8617174
DOI:: 10.1038/s41467-021-26805-8
PMID:: 34824211
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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.
(© 2021. The Author(s).)

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