Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.
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Butler, Adam P
Springer Science and Business Media LLC
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Álvarez, E. G., Demeulemeester, J., Otero, P., Jolly, C., García-Souto, D., Pequeño-Valtierra, A., Zamora, J., et al. (2021). Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.. Nat Commun, 12 (1) https://doi.org/10.1038/s41467-021-26805-8
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.
Article, /631/67/1858, /631/208/69, /631/67/1504/1610/4029, /45/23, /14/32, article
External DOI: https://doi.org/10.1038/s41467-021-26805-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331422