Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas

Jessica Zucman-Rossi and colleagues identify clonal integrations of adeno-associated virus type 2 (AAV2) in hepatocellular carcinomas. These AAV2 integrations occurred within known cancer driver genes, suggesting a pathogenic role of AAV2 in these patients. Hepatocellular carcinomas (HCCs) are liver...

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Bibliographic Details
Published in:Nature genetics Vol. 47; no. 10; pp. 1187 - 1193
Main Authors: Nault, Jean-Charles, Datta, Shalini, Imbeaud, Sandrine, Franconi, Andrea, Mallet, Maxime, Couchy, Gabrielle, Letouzé, Eric, Pilati, Camilla, Verret, Benjamin, Blanc, Jean-Frédéric, Balabaud, Charles, Calderaro, Julien, Laurent, Alexis, Letexier, Mélanie, Bioulac-Sage, Paulette, Calvo, Fabien, Zucman-Rossi, Jessica
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.10.2015
Nature Publishing Group
Subjects:
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692/699/67/1504
Agriculture
Animal Genetics and Genomics
Biomedicine
Cancer Research
Carcinoma, Hepatocellular - genetics
Cell cycle
Cyclin A2 - genetics
Cyclin E - genetics
Dependovirus - genetics
Dependoviruses
Development and progression
Disease susceptibility
Gene Function
Gene mutation
Genetic aspects
Genomes
Health aspects
Hepatitis B
Hepatocellular carcinoma
Human Genetics
Humans
Identification and classification
Infections
Kinases
letter
Liver cancer
Liver cirrhosis
Liver Neoplasms - genetics
Molecular Sequence Data
Mutagenesis
Mutagenesis, Insertional
Mutation
Oncogene Proteins - genetics
Risk factors
Telomerase
Telomerase - genetics
TNF-Related Apoptosis-Inducing Ligand - genetics
Tumor necrosis factor-TNF
Tumors
Virus Integration
Viruses
ISSN:1061-4036, 1546-1718, 1546-1718
Online Access:Get full text
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Summary:Jessica Zucman-Rossi and colleagues identify clonal integrations of adeno-associated virus type 2 (AAV2) in hepatocellular carcinomas. These AAV2 integrations occurred within known cancer driver genes, suggesting a pathogenic role of AAV2 in these patients. Hepatocellular carcinomas (HCCs) are liver tumors related to various etiologies, including alcohol intake and infection with hepatitis B (HBV) or C (HCV) virus. Additional risk factors remain to be identified, particularly in patients who develop HCC without cirrhosis. We found clonal integration of adeno-associated virus type 2 (AAV2) in 11 of 193 HCCs. These AAV2 integrations occurred in known cancer driver genes, namely CCNA2 (cyclin A2; four cases), TERT (telomerase reverse transcriptase; one case), CCNE1 (cyclin E1; three cases), TNFSF10 (tumor necrosis factor superfamily member 10; two cases) and KMT2B (lysine-specific methyltransferase 2B; one case), leading to overexpression of the target genes. Tumors with viral integration mainly developed in non-cirrhotic liver (9 of 11 cases) and without known risk factors (6 of 11 cases), suggesting a pathogenic role for AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated with oncogenic insertional mutagenesis in human HCC.
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ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/ng.3389