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. 2015 Oct;47(10):1187-93.
doi: 10.1038/ng.3389. Epub 2015 Aug 24.

Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas

Jean-Charles Nault  1   2   3   4   5 , Shalini Datta  1   2   3   4 , Sandrine Imbeaud  1   2   3   4 , Andrea Franconi  1   2   3   4 , Maxime Mallet  1   2   3   4 , Gabrielle Couchy  1   2   3   4 , Eric Letouzé  1   2   3   4 , Camilla Pilati  1   2   3   4 , Benjamin Verret  1   4 , Jean-Frédéric Blanc  6   7   8 , Charles Balabaud  7   8 , Julien Calderaro  1   2   3   4   9 , Alexis Laurent  10   11 , Mélanie Letexier  12 , Paulette Bioulac-Sage  7   8   13 , Fabien Calvo  1   2   3   4   14 , Jessica Zucman-Rossi  1   2   3   4   15
Affiliations

Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas

Jean-Charles Nault et al. Nat Genet. 2015 Oct.

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.

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Comment in

  • Adeno-associated virus finds its disease.
    Russell DW, Grompe M. Russell DW, et al. Nat Genet. 2015 Oct;47(10):1104-5. doi: 10.1038/ng.3407. Nat Genet. 2015. PMID: 26417859 Free PMC article.
  • Adeno-Associated Virus Type 2 and Hepatocellular Carcinoma?
    Berns KI, Byrne BJ, Flotte TR, Gao G, Hauswirth WW, Herzog RW, Muzyczka N, VandenDriessche T, Xiao X, Zolotukhin S, Srivastava A. Berns KI, et al. Hum Gene Ther. 2015 Dec;26(12):779-81. doi: 10.1089/hum.2015.29014.kib. Hum Gene Ther. 2015. PMID: 26690810 Free PMC article. No abstract available.
  • AAV2 and Hepatocellular Carcinoma.
    Nault JC, Datta S, Imbeaud S, Franconi A, Mallet M, Couchy G, Letouzé E, Pilati C, Verret B, Blanc JF, Balabaud C, Calderaro J, Laurent A, Letexier M, Bioulac-Sage P, Calvo F, Zucman-Rossi J. Nault JC, et al. Hum Gene Ther. 2016 Mar;27(3):211-3. doi: 10.1089/hum.2016.002. Hum Gene Ther. 2016. PMID: 26935016 No abstract available.

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