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

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cam.issuedOnline2021-11-25
dc.contributor.authorÁlvarez, Eva G
dc.contributor.authorDemeulemeester, Jonas
dc.contributor.authorOtero, Paula
dc.contributor.authorJolly, Clemency
dc.contributor.authorGarcía-Souto, Daniel
dc.contributor.authorPequeño-Valtierra, Ana
dc.contributor.authorZamora, Jorge
dc.contributor.authorTojo, Marta
dc.contributor.authorTemes, Javier
dc.contributor.authorBaez-Ortega, Adrian
dc.contributor.authorRodriguez-Martin, Bernardo
dc.contributor.authorOitaben, Ana
dc.contributor.authorBruzos, Alicia L
dc.contributor.authorMartínez-Fernández, Mónica
dc.contributor.authorHaase, Kerstin
dc.contributor.authorZumalave, Sonia
dc.contributor.authorAbal, Rosanna
dc.contributor.authorRodríguez-Castro, Jorge
dc.contributor.authorRodriguez-Casanova, Aitor
dc.contributor.authorDiaz-Lagares, Angel
dc.contributor.authorLi, Yilong
dc.contributor.authorRaine, Keiran M
dc.contributor.authorButler, Adam P
dc.contributor.authorOtero, Iago
dc.contributor.authorOno, Atsushi
dc.contributor.authorAikata, Hiroshi
dc.contributor.authorChayama, Kazuaki
dc.contributor.authorUeno, Masaki
dc.contributor.authorHayami, Shinya
dc.contributor.authorYamaue, Hiroki
dc.contributor.authorMaejima, Kazuhiro
dc.contributor.authorBlanco, Miguel G
dc.contributor.authorForns, Xavier
dc.contributor.authorRivas, Carmen
dc.contributor.authorRuiz-Bañobre, Juan
dc.contributor.authorPérez-Del-Pulgar, Sofía
dc.contributor.authorTorres-Ruiz, Raúl
dc.contributor.authorRodriguez-Perales, Sandra
dc.contributor.authorGaraigorta, Urtzi
dc.contributor.authorCampbell, Peter J
dc.contributor.authorNakagawa, Hidewaki
dc.contributor.authorVan Loo, Peter
dc.contributor.authorTubio, Jose MC
dc.contributor.orcidÁlvarez, Eva G [0000-0002-3522-5088]
dc.contributor.orcidDemeulemeester, Jonas [0000-0002-2660-2478]
dc.contributor.orcidOtero, Paula [0000-0001-5614-1468]
dc.contributor.orcidGarcía-Souto, Daniel [0000-0002-0997-8799]
dc.contributor.orcidTemes, Javier [0000-0003-3370-4728]
dc.contributor.orcidRodriguez-Martin, Bernardo [0000-0003-4693-3140]
dc.contributor.orcidOitaben, Ana [0000-0002-4877-6145]
dc.contributor.orcidBruzos, Alicia L [0000-0003-4362-545X]
dc.contributor.orcidHaase, Kerstin [0000-0002-0944-5618]
dc.contributor.orcidZumalave, Sonia [0000-0002-2108-1861]
dc.contributor.orcidRodríguez-Castro, Jorge [0000-0003-2912-9601]
dc.contributor.orcidRodriguez-Casanova, Aitor [0000-0002-9828-3613]
dc.contributor.orcidRaine, Keiran M [0000-0002-5634-1539]
dc.contributor.orcidOtero, Iago [0000-0002-7924-693X]
dc.contributor.orcidBlanco, Miguel G [0000-0002-2883-7326]
dc.contributor.orcidRuiz-Bañobre, Juan [0000-0003-0755-4295]
dc.contributor.orcidPérez-Del-Pulgar, Sofía [0000-0002-9890-300X]
dc.contributor.orcidTorres-Ruiz, Raúl [0000-0001-9606-0398]
dc.contributor.orcidRodriguez-Perales, Sandra [0000-0001-7221-3636]
dc.contributor.orcidGaraigorta, Urtzi [0000-0002-0683-5725]
dc.contributor.orcidCampbell, Peter J [0000-0002-3921-0510]
dc.contributor.orcidVan Loo, Peter [0000-0003-0292-1949]
dc.contributor.orcidTubio, Jose MC [0000-0003-3540-2459]
dc.date.accessioned2022-01-10T11:44:04Z
dc.date.available2022-01-10T11:44:04Z
dc.date.issued2021-11-25
dc.date.updated2022-01-10T11:44:04Z
dc.description.abstractMost 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.
dc.identifier.doi10.17863/CAM.79917
dc.identifier.eissn2041-1723
dc.identifier.issn2041-1723
dc.identifier.otherPMC8617174
dc.identifier.other34824211
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332468
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41467-021-26805-8
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2041-1723
dc.sourcenlmid: 101528555
dc.subjectCarcinoma, Hepatocellular
dc.subjectDNA, Viral
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectGenome, Human
dc.subjectHepatitis B virus
dc.subjectHumans
dc.subjectLiver Neoplasms
dc.subjectVirus Integration
dc.subjectWhole Genome Sequencing
dc.titleAberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.
dc.typeArticle
dcterms.dateAccepted2021-10-22
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume12
pubs.funder-project-idEuropean Research Council (716290)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-021-26805-8

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