Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas.
Jean-Charles NaultShalini DattaSandrine ImbeaudAndrea FranconiMaxime MalletGabrielle CouchyEric LetouzéCamilla PilatiBenjamin VerretJean-Frédéric BlancCharles BalabaudJulien CalderaroAlexis LaurentMélanie LetexierPaulette Bioulac-SageFabien CalvoJessica Zucman-RossiPublished in: Nature genetics (2015)
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.
Keyphrases
- gene therapy
- risk factors
- endothelial cells
- crispr cas
- end stage renal disease
- induced pluripotent stem cells
- newly diagnosed
- genome wide
- cell cycle
- ejection fraction
- hepatitis b virus
- genome wide identification
- sars cov
- high grade
- prognostic factors
- transcription factor
- chronic kidney disease
- pluripotent stem cells
- rheumatoid arthritis
- cell proliferation
- dna methylation
- human immunodeficiency virus
- bioinformatics analysis
- gene expression
- hiv infected
- weight gain
- liver failure
- disease virus
- body mass index
- drug induced
- alcohol consumption
- cell death