Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architectureMore about Open Access at the Crick
Authors listEva 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
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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.
Journal Nature Communications