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

Author:

Álvarez Eva G.,Demeulemeester Jonas,Jolly Clemency,García-Souto Daniel,Otero Paula,Pequeño Ana,Zamora Jorge,Tojo Marta,Temes Javier,Baez-Ortega Adrian,Rodríguez-Martín Bernardo,Li Yilong,Oitaben Ana,Bruzos Alicia L.,Martínez-Fernández Mónica,Haase Kerstin,Santamarina Martin,Zumalave Sonia,Abal Rosanna,Rodríguez-Castro Jorge,Rodriguez-Casanova Aitor,Diaz-Lagares Angel,Raine Keiran,Butler Adam P.,Ono Atsuhi,Aikata Hiroshi,Chayama Kazuaki,Ueno Masaki,Hayami Shinya,Yamaue Hiroki,Blanco Miguel G.,Forns Xavier,Rivas Carmen,Pérez-del-Pulgar Sofía,Torres-Ruiz Raúl,Rodríguez Perales Sandra,Garaigorta Urtzi,Nakagawa Hidewaki,Campbell Peter J.,Van Loo Peter,Tubio Jose M. C.

Abstract

Most cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. There are different mutational mechanisms causing structural variation, some of which are specific to particular cancer types. 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 and megabase-size telomeric deletions. This aberrant mutational process, present in at least 8% of all HCC tumours, is active early during liver cancer evolution and can provide the driver rearrangements that a cancer clone requires to survive and grow.

Publisher

Cold Spring Harbor Laboratory

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