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Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas.

Nat. Genet.. 2015;

NaultJean-Charles，DattaShalini，ImbeaudSandrine，FranconiAndrea，MalletMaxime，CouchyGabrielle，LetouzéEric，PilatiCamilla，VerretBenjamin，BlancJean-Frédéric，BalabaudCharles，CalderaroJulien，LaurentAlexis，LetexierMélanie，Bioulac-SagePaulette，CalvoFabien，Zucman-RossiJes

Products/Services Used	Details	Operation
Custom Vector Construction	The 208-bp AAV2 sequence along with the additional 7 bp identified in CHC985T was inserted into the pGL3 vector (Supplementary Fig. 1a) in the TERT promoter (500 bp upstream of the TSS) kindly provided by X. Mayol (Institut Hospital del Mar d’Investigacions Mèdiques) by nucleotide synthesis (GenScript). The 210-bp AAV2 sequence from CHC2557T and the 301-bp AAV2 sequence along with 2 bp from CHC1602T were cloned into pmirGLO vector containing a 132-bp fragment of the 3′ UTR of TNFSF10 (CHC2557T) or the entire 3′ UTR of TNFSF10 (984 bp; CHC1602T) (described in Fig. 3) after synthesis by GenScript (Supplementary Fig. 1b).	Get A Quote

摘要

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 ... More