Adeno-associated virus in the liver: natural history and consequences in tumor development

Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (40-80%). AAV infection has long been considered as non-pathogenic1, however few years ago we reported for the first time recurrent clonal AAV2 insertion in the pathogenesis of human hepatocellular carcinoma (HCC) developed on normal liver. These clonal viral insertions target cancer driver genes, including CCNA2, CCNE1, TERT, TNFSF10 and MLL4, leading to their overexpression. The viral inserted sequences involved in almost all the cases the 3’ inverse tandem repeat (ITR) of AAV2, which is important for virus integration in host DNA and exhibits a promoter/enhancer activity. Here, we used RNA sequencing (RNA-seq) to investigate their functional impact on the tissue, such as fusion transcript generation events.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 2 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001004484	Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (35-80%). Recurrent clonal AAV2 insertions are associated with the pathogenesis of rare human hepatocellular carcinoma (HCC) developed on normal liver. This study aimed to characterize the natural history of AAV infection in the liver and its consequence in tumor development. In silico analyses using viral capture data explored viral variants and new clonal insertions. Clonal AAV insertions were positive selected during HCC development on non-cirrhotic liver challenging the notion of AAV as a non-pathogenic virus.	Illumina HiSeq 2000	20

Publications	Citations
Adeno-associated virus in the liver: natural history and consequences in tumour development. La Bella T, Imbeaud S, Peneau C, Mami I, Datta S, Bayard Q, Caruso S, Hirsch TZ, Calderaro J, Morcrette G, Guettier C, Paradis V, Amaddeo G, Laurent A, Possenti L, Chiche L, Bioulac-Sage P, Blanc JF, Letouze E, Nault JC, Zucman-Rossi J. Gut 69: 2020 737-747	57
Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocellular carcinoma. Péneau C, Imbeaud S, La Bella T, Hirsch TZ, Caruso S, Calderaro J, Paradis V, Blanc JF, Letouzé E, Nault JC, Amaddeo G, Zucman-Rossi J. Gut 71: 2022 616-626	79