ArticleNature communications2021
Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
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41 citing papers in PubMed, 53 citations in OpenAlex.
- Viral persistence and host-state remodeling in virus-associated cancers.Archives of microbiology · 2026Review
- Virus infections and cancers: from mechanisms to therapeutics.Molecular biomedicine · 2026Review
- Beyond silencing: integrative multi-omics and spatial profiling unravel the systems-level role of piRNAs in HBV-driven Hepatocarcinogenesis.Molecular biology reports · 2026Review
- Clinical applications of immunogenomics in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- Long-term Dynamic Virological Response Patterns and Clinical Outcomes in Hepatitis B Virus-related Cirrhosis: A Real-world 10-year Cohort Study.Journal of clinical and translational hepatology · 2026Article
- Current advances and future directions in the management of HBV-related hepatocellular carcinoma.Gastroenterology report · 2026Review
- Messenger RNA therapy in bone and joint diseases: Rationale, delivery systems, and applications.Biomaterials translational · 2026Article
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- Long-read sequencing reveals HBV integration patterns and oncogenic impact on early-onset hepatocellular carcinoma.Genome research · 2025Article
- Giant endogenous viral elements in the genome of the model protistJournal of virology · 2025Article
- SAVANA: reliable analysis of somatic structural variants and copy number aberrations using long-read sequencing.Nature methods · 2025Article
- Cancer immunotherapy clinical trials to support urgently needed access in low- and middle-income countries: a report from the SITC global access and impact committee.Journal for immunotherapy of cancer · 2025Review
- Multisite long-read sequencing reveals the early contributions of somatic structural variations to HBV-related hepatocellular carcinoma tumorigenesis.Genome research · 2025Article
- HBV-Induced Carcinogenesis: Mechanisms, Correlation With Viral Suppression, and Implications for Treatment.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Review
- Hepatocellular carcinoma among patients with chronic hepatitis B in the indeterminate phase.Journal of viral hepatitis · 2024Review
- The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers.International journal of molecular sciences · 2024Review
- The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.Biomarker research · 2024Review
- Canadian Association for the Study of the Liver Single Topic Conference on Hepatitis B Virus: 'Progress toward hepatitis B elimination in Canada'.Canadian liver journal · 2024Article
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Authors and funding
43 authors at 12 institutions in 4 countries.
Eva G ÁlvarezCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0002-3522-5088
Jonas Demeulemeester *The Francis Crick Institute, London, NW1 1AT, UK.ORCID http://orcid.org/0000-0002-2660-2478
Paula Otero *Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0001-5614-1468
Clemency Jolly *The Francis Crick Institute, London, NW1 1AT, UK.
Daniel García-Souto *Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0002-0997-8799
Ana Pequeño-ValtierraCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Jorge ZamoraCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Marta TojoThe Biomedical Research Centre (CINBIO), Universidade de Vigo, Vigo, 36310, Spain.
Javier TemesCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0003-3370-4728
Adrian Baez-OrtegaDepartment of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES, UK.
Bernardo Rodriguez-MartinCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0003-4693-3140
Ana OitabenCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0002-4877-6145
Alicia L BruzosCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0003-4362-545X
Mónica Martínez-FernándezCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Kerstin HaaseThe Francis Crick Institute, London, NW1 1AT, UK.ORCID http://orcid.org/0000-0002-0944-5618
Sonia ZumalaveCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0002-2108-1861
Rosanna AbalCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Jorge Rodríguez-CastroCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0003-2912-9601
Aitor Rodriguez-CasanovaCancer 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.ORCID http://orcid.org/0000-0002-9828-3613
Angel Diaz-LagaresCancer 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.
Yilong LiWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Keiran M RaineWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.ORCID http://orcid.org/0000-0002-5634-1539
Adam P ButlerWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Iago OteroCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0002-7924-693X
Atsushi OnoDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hiroshi AikataDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Kazuaki ChayamaCollaborative Research Laboratory of Medical Innovation, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Masaki UenoDepartment of Surgery II, Wakayama Medical University, Wakayama, Japan.
Shinya HayamiDepartment of Surgery II, Wakayama Medical University, Wakayama, Japan.
Hiroki YamaueDepartment of Surgery II, Wakayama Medical University, Wakayama, Japan.
Kazuhiro MaejimaRIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
Miguel G BlancoCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0002-2883-7326
Xavier FornsLiver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
Carmen RivasCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.
Juan Ruiz-BañobreCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain.ORCID http://orcid.org/0000-0003-0755-4295
Sofía Pérez-Del-PulgarLiver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.ORCID http://orcid.org/0000-0002-9890-300X
Raúl Torres-RuizMolecular Cytogenetics and Genome Engineering Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0001-9606-0398
Sandra Rodriguez-PeralesMolecular Cytogenetics and Genome Engineering Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0001-7221-3636
Urtzi Garaigorta *Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología - Consejo Superior de Investigaciones Científicas (CNB - CSIC), Madrid, 28049, Spain.ORCID http://orcid.org/0000-0002-0683-5725
Peter J Campbell *Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.ORCID http://orcid.org/0000-0002-3921-0510
Hidewaki Nakagawa *RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.
Peter Van Loo *The Francis Crick Institute, London, NW1 1AT, UK.ORCID http://orcid.org/0000-0003-0292-1949
Jose M C TubioCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, 15706, Spain. jose.mc.tubio@usc.es.ORCID http://orcid.org/0000-0003-3540-2459
Universidade de Santiago de Compostela · ESThe Francis Crick Institute · GBHiroshima University · JPWakayama Medical University · JPWellcome Sanger Institute · GBHospital Clínic de Barcelona · ESInstituto de Investigación Sanitaria de Santiago · ESRIKEN Center for Integrative Medical Sciences · JPSpanish National Cancer Research Centre · ESUniversity of Cambridge · GBConsejo Superior de Investigaciones Científicas · ESUniversidade de Vigo · ES
Funding
Medical Research Council MR/L016311/1Wellcome Trust FC001202
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.
Indexed as
DNA, ViralGenome, HumanCarcinoma, HepatocellularGene Expression Regulation, NeoplasticHepatitis B virusHumansLiver NeoplasmsVirus IntegrationWhole Genome SequencingDNA, Viral
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