1. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas
- Author
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Jean-Frédéric Blanc, Benjamin Verret, Eric Letouzé, Sandrine Imbeaud, Jessica Zucman-Rossi, Jean-Charles Nault, Gabrielle Couchy, Charles Balabaud, Alexis Laurent, Maxime Mallet, Camilla Pilati, Paulette Bioulac-Sage, Shalini Datta, Julien Calderaro, Andrea Franconi, Mélanie Letexier, and Fabien Calvo
- Subjects
Cyclin E ,viruses ,Cyclin D ,Cancer ,Biology ,Hepatitis B ,HCCS ,medicine.disease ,Virology ,digestive system diseases ,Insertional mutagenesis ,Cyclin E1 ,Genetics ,medicine ,Cancer research ,biology.protein ,Cyclin A2 - Abstract
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.
- Published
- 2015
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