Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture
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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-Martin Ana Oitaben Alicia L Bruzos Mónica Martínez-Fernández Kerstin Haase Sonia Zumalave Rosanna Abal Jorge Rodríguez-Castro Aitor Rodriguez-Casanova Angel Diaz-Lagares Yilong Li Keiran M Raine Adam P Butler Iago Otero Atsushi Ono Hiroshi Aikata Kazuaki Chayama Masaki Ueno Shinya Hayami Hiroki Yamaue Kazuhiro Maejima Miguel G Blanco Xavier Forns Carmen Rivas Juan Ruiz-Bañobre Sofía Pérez-del-Pulgar Raúl Torres-Ruiz Sandra Rodriguez-Perales Urtzi Garaigorta Peter J Campbell Hidewaki Nakagawa Peter Van Loo Jose MC Tubio Toggle all authors (43)
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.
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Journal Nature Communications
Volume 12
Pages 6910
Available online
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Publisher website (DOI) 10.1038/s41467-021-26805-8
Europe PubMed Central 34824211
Pubmed 34824211
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