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

Bibliographic Details
Title: Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.
Authors: Álvarez, Eva G., Demeulemeester, Jonas, Otero, Paula, Jolly, Clemency, García-Souto, Daniel, Pequeño-Valtierra, Ana, Zamora, Jorge, Tojo, Marta, Temes, Javier, Baez-Ortega, Adrian, Rodriguez-Martin, Bernardo, Oitaben, Ana, Bruzos, Alicia L., Martínez-Fernández, Mónica, Haase, Kerstin, Zumalave, Sonia, Abal, Rosanna, Rodríguez-Castro, Jorge, Rodriguez-Casanova, Aitor, Diaz-Lagares, Angel
Source: Nature Communications; 11/25/2021, Vol. 12 Issue 1, p1-12, 12p
Subject Terms: HEPATITIS B virus, DNA viruses, HEPATOCELLULAR carcinoma, TUMOR suppressor genes, LIVER cancer
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. [ABSTRACT FROM AUTHOR]
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Database: Complementary Index
More Details
ISSN:20411723
DOI:10.1038/s41467-021-26805-8
Published in:Nature Communications
Language:English