Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 11 2021
25 11 2021
Historique:
received:
08
04
2021
accepted:
22
10
2021
entrez:
26
11
2021
pubmed:
27
11
2021
medline:
4
1
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34824211
doi: 10.1038/s41467-021-26805-8
pii: 10.1038/s41467-021-26805-8
pmc: PMC8617174
doi:
Substances chimiques
DNA, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6910Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001202
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L016311/1
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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