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- Title
Insertional Oncogenesis by Non-Acute Retroviruses: Implications for Gene Therapy.
- Authors
Hung Fan; Johnson, Chassidy
- Abstract
Retro viruses cause cancers in a variety of animals and humans. Research on retro viruses has provided important insights into mechanisms of oncogenesis in humans, including the discovery of viral oncogenes and cellular proto-oncogenes. The subject of this review is the mechanisms by which retro viruses that do not carry oncogenes (non-acute retro viruses) cause cancers. The common theme is that these tumors result from insertional activation of cellular proto-oncogenes by integration of viral DNA. Early research on insertional activation of proto-oncogenes in virus induced tumors is reviewed. Research on non-acute retro viruses has led to the discovery of new proto-oncogenes through searches for common insertion sites (CISs) in virus-induced tumors. Cooperation between different proto-oncogenes in development of tumors has been elucidated through the study of retrovirus-induced tumors, and retro viral infection of genetically susceptible mice (retro viral tagging) has been used to identify cellular proto-oncogenes active in specific oncogenic pathways. The pace of proto-oncogene discovery has been accelerated by technical advances including PCR cloning of viral integration sites, the availability of the mouse genome sequence, and high throughput DNA sequencing. Insertional activation has proven to be a significant risk in gene therapy trials to correct genetic defects with retroviral vectors. Studies on non-acute retroviral oncogenesis provide insight into the potential risks, and the mechanisms of oncogenesis.
- Subjects
VIRUS research; CARCINOGENESIS; ONCOGENES; ONCOGENIC DNA viruses; LABORATORY mice
- Publication
Viruses (1999-4915), 2011, Vol 3, Issue 4, p398
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v3040398