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

Demeulemeester, Jonas  ORCID logo  https://orcid.org/0000-0002-2660-2478
Jolly, Clemency 
García-Souto, Daniel  ORCID logo  https://orcid.org/0000-0002-0997-8799

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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.

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Carcinoma, Hepatocellular, DNA, Viral, Gene Expression Regulation, Neoplastic, Genome, Human, Hepatitis B virus, Humans, Liver Neoplasms, Virus Integration, Whole Genome Sequencing
Journal Title
Nat Commun
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Springer Science and Business Media LLC
European Research Council (716290)