Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. JC Nault, S Datta, S Imbeaud, A Franconi, M Mallet, G Couchy, E Letouzé, C Pilati, B Verret, JF Blanc, C Balabaud, J Calderaro, A Laurent, M Letexier, P Bioulac-Sage, F Calvo, J Zucman-Rossi. Nat Genet 2015 Oct;47(10):1187-1193. “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.” Of the 11 patients, one had HCV, one HBV plus alcohol, and three tumors were alcohol-related. Three patients were female (Supplementary Table 2).