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Insertional oncogenesis by non-acute retroviruses: implications for gene therapy

Hung Fan1, Chassidy Johnson

  • 1Department of Molecular Biology and Biochemistry, Cancer Research Institute, University of California, Irvine, CA 92697, USA. hyfan@uci.edu

Viruses
|October 14, 2011
PubMed

Insights

Non-acute retroviruses cause cancer by integrating viral DNA into host cells, activating proto-oncogenes. This review details insertional activation mechanisms and proto-oncogene discovery, crucial for understanding oncogenesis and gene therapy risks.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Retroviruses are known to cause cancers in humans and animals.
  • Research has illuminated oncogenesis mechanisms, including viral and cellular proto-oncogenes.
  • Non-acute retroviruses, lacking oncogenes, induce tumors through insertional activation of proto-oncogenes.

Purpose of the Study:

  • To review the mechanisms by which non-acute retroviruses cause cancer.
  • To highlight the role of insertional activation of cellular proto-oncogenes.
  • To discuss the discovery of proto-oncogenes and their cooperation in tumorigenesis.

Main Methods:

  • Review of early research on insertional activation in virus-induced tumors.
  • Identification of common insertion sites (CISs) to discover new proto-oncogenes.
  • Retroviral tagging in susceptible mice to identify active proto-oncogenes in oncogenic pathways.
  • Utilizing technical advances like PCR cloning, mouse genome sequence, and high-throughput sequencing.

Main Results:

  • Insertional activation of proto-oncogenes by viral DNA integration is a key mechanism.
  • Discovery of novel proto-oncogenes through CIS analysis.
  • Elucidation of proto-oncogene cooperation in tumor development.
  • Identification of cellular proto-oncogenes involved in specific oncogenic pathways.

Conclusions:

  • Non-acute retroviral oncogenesis is primarily driven by insertional activation of proto-oncogenes.
  • Studies have significantly advanced the discovery of proto-oncogenes and understanding of oncogenic pathways.
  • Insertional activation poses risks in gene therapy using retroviral vectors, necessitating careful consideration of oncogenesis mechanisms.
Keywords:
gene therapynon-acute retrovirusoncogeneoncogenesisproto-oncogeneretroviral vectorretrovirus

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