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

Autor: Hidewaki Nakagawa, Hiroshi Aikata, Mónica Martínez-Fernández, Atsushi Ono, Marta Tojo, Peter J. Campbell, Adrian Baez-Ortega, Kerstin Haase, Jonas Demeulemeester, Adam Butler, Xavier Forns, Rosanna Abal, Keiran Raine, Javier Temes, Urtzi Garaigorta, Daniel García-Souto, Carmen Rivas, Aitor Rodriguez-Casanova, Eva G. Alvarez, Sonia Zumalave, Jorge Zamora, Hiroki Yamaue, Clemency Jolly, Yang Li, Peter Van Loo, Jose M. C. Tubio, Kazuaki Chayama, Iago Otero, Sofía Pérez-del-Pulgar, Masaki Ueno, Miguel Blanco, Shinya Hayami, Sandra Rodriguez-Perales, Kazuhiro Maejima, Jorge Rodríguez-Castro, Angel Diaz-Lagares, Raúl Torres-Ruiz, Ana Pequeño-Valtierra, Juan Ruiz-Bañobre, Ana Oitaben, Bernardo Rodriguez-Martin, Paula Otero, Alicia L. Bruzos
Přispěvatelé: Álvarez, Eva G [0000-0002-3522-5088], Demeulemeester, Jonas [0000-0002-2660-2478], Otero, Paula [0000-0001-5614-1468], García-Souto, Daniel [0000-0002-0997-8799], Temes, Javier [0000-0003-3370-4728], Rodriguez-Martin, Bernardo [0000-0003-4693-3140], Oitaben, Ana [0000-0002-4877-6145], Bruzos, Alicia L [0000-0003-4362-545X], Haase, Kerstin [0000-0002-0944-5618], Zumalave, Sonia [0000-0002-2108-1861], Rodríguez-Castro, Jorge [0000-0003-2912-9601], Rodriguez-Casanova, Aitor [0000-0002-9828-3613], Raine, Keiran M [0000-0002-5634-1539], Otero, Iago [0000-0002-7924-693X], Blanco, Miguel G [0000-0002-2883-7326], Ruiz-Bañobre, Juan [0000-0003-0755-4295], Pérez-Del-Pulgar, Sofía [0000-0002-9890-300X], Torres-Ruiz, Raúl [0000-0001-9606-0398], Rodriguez-Perales, Sandra [0000-0001-7221-3636], Garaigorta, Urtzi [0000-0002-0683-5725], Campbell, Peter J [0000-0002-3921-0510], Van Loo, Peter [0000-0003-0292-1949], Tubio, Jose MC [0000-0003-3540-2459], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2021
Předmět:
LIVER
Hepatocellular carcinoma
General Physics and Astronomy
medicine.disease_cause
Genome
631/67/1858
Ecology
Evolution & Ethology
Cancer genomics
Tumour virus infections
631/208/69
Human Biology & Physiology
Multidisciplinary
Liver Neoplasms
ASSOCIATION
READ ALIGNMENT
TRANSLOCATION
Multidisciplinary Sciences
Gene Expression Regulation
Neoplastic
Science & Technology - Other Topics
Liver cancer
Genetics & Genomics
Hepatitis B virus
Carcinoma
Hepatocellular
Science
Virus Integration
631/67/1504/1610/4029
45/23
Biology
General Biochemistry
Genetics and Molecular Biology
Virus
Article
14/32
CHROMOSOMES
medicine
Humans
Gene
Computational & Systems Biology
Science & Technology
Whole Genome Sequencing
MUTATIONS
Genome
Human
Cancer
General Chemistry
Tumour Biology
medicine.disease
digestive system diseases
DNA
Viral
Cancer research
Carcinogenesis
Zdroj: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021)
ISSN: 2041-1723
Popis: 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.
Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient samples to study the timing and alterations induced by HBV insertions.
Databáze: OpenAIRE
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