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

Author

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, and Jose M. C. Tubio

Subjects
Science
Abstract

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.

Published
2021
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2. Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture

Author

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, 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], and Apollo - University of Cambridge Repository

Subjects
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
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., 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.

Published
2021

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