AAV基因治疗再遇雪霜-AAV2有引发肝癌的可能性

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Nature Genetics  8月发文Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas

• Jean-Charles Nault,
• Shalini Datta,
• Sandrine Imbeaud,
• Andrea Franconi,
• Maxime Mallet,
• Gabrielle Couchy,
• Eric Letouzé,
• Camilla Pilati,
• Benjamin Verret,
• Jean-Frédéric Blanc,
• Charles Balabaud,
• Julien Calderaro,
• Alexis Laurent,
• Mélanie Letexier,
• Paulette Bioulac-Sage,
• Fabien Calvo
• & Jessica Zucman-Rossi
  

• Affiliations
• Contributions
• Corresponding author
  

Nature Genetics 47, 1187–1193 (2015) doi:10.1038/ng.3389Received 11 February 2015 Accepted 31 July 2015 Published online 24 August 2015

摘要如下：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.
学术界早在二十年前就有过AAV会引起致癌的猜想，而关于其讨论研究一直持续了近十年，想不到一直没有一些非常针对性的证据的时候来了这么篇文章。

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病毒作为基因治疗载体还是不太让人放心啊