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Adeno-associated virus type 2 as an oncogenic virus in human hepatocellular carcinoma

Jean-Charles Nault1, Shalini Datta2, Sandrine Imbeaud2

  • 1Inserm, UMR-1162, Génomique fonctionnelle des Tumeurs solides, Equipe Labellisée Ligue Contre le Cancer, Paris, F-75010 France; Université Paris Descartes, Labex Immuno-Oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; Université Paris 13, Sorbonne Paris Cité, UFR SMBH, F-93000 Bobigny, France; Université Paris Diderot, F-75013 Paris; APHP, Hôpitaux Universitaires Paris - Seine Saint-Denis, Site Jean Verdier, Pôle d'Activité Cancérologique Spécialisée, Service d'Hépatologie, F-93143 Bondy, France.

Molecular & Cellular Oncology
|June 17, 2016
PubMed

Insights

Adeno-associated virus type 2 (AAV2) DNA integration was found in hepatocellular carcinoma (HCC) cases. This viral DNA insertional mutagenesis occurred in key cancer driver genes, suggesting a novel role for AAV2 in liver cancer development.

Area of Science:

  • Hepatology
  • Virology
  • Oncology

Background:

  • Adeno-associated virus type 2 (AAV2) is a defective DNA virus.
  • AAV2 was previously considered non-pathogenic.
  • Hepatocellular carcinoma (HCC) is a primary liver cancer.

Purpose of the Study:

  • To investigate the potential role of AAV2 in the development of HCC.
  • To identify if AAV2 integrates into the host genome in HCC cases.

Main Methods:

  • Analysis of tumor samples from HCC patients.
  • Detection of viral DNA integration using molecular techniques.
  • Identification of host genes affected by viral insertion.

Main Results:

  • Somatic AAV2 integration was identified in a subset of 11 HCC cases.
  • Integrations were found in normal liver tissue without known predisposing factors.
  • Recurrent insertional mutagenesis occurred in cancer driver genes including TERT, CCNA2, CCNE1, TNFSF10, and KMT2B.

Conclusions:

  • Somatic AAV2 integration is associated with HCC development.
  • AAV2 can act as an insertional mutagen in liver cancer.
  • This finding suggests a novel pathogenic role for AAV2 in human cancer.
Keywords:
Adeno-associated virus type 2TERTgene therapyhepatocellular carcinomainsertional mutagenesis

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