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

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 | Jose M C Tubio
Nature communications | 2021

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.

Pubmed ID: 34824211 RIS Download

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
  • Agency: Arthritis Research UK, United Kingdom
    Id: FC001202
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L016311/1

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Synapse (tool)

RRID:SCR_006307

A cloud-based collaborative platform which co-locates data, code, and computing resources for analyzing genome-scale data and seamlessly integrates these services allowing scientists to share and analyze data together. Synapse consists of a web portal integrated with the R/Bioconductor statistical package and will be integrated with additional tools. The web portal is organized around the concept of a Project which is an environment where you can interact, share data, and analysis methods with a specific group of users or broadly across open collaborations. Projects provide an organizational structure to interact with data, code and analyses, and to track data provenance. A project can be created by anyone with a Synapse account and can be shared among all Synapse users or restricted to a specific team. Public data projects include the Synapse Commons Repository (SCR) (syn150935) and the metaGenomics project (syn275039). The SCR provides access to raw data and phenotypic information for publicly available genomic data sets, such as GEO and TCGA. The metaGenomics project provides standardized preprocessed data and precomputed analysis of the public SCR data.

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ICGC Data Portal (tool)

RRID:SCR_021722

Portal provides tools for visualizing, querying, and downloading cancer data, which is released on quarterly schedule.

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