Oncogenes at viral integration sites.

Most retroviruses are innocuous to the cells they infect and do not encode transforming genes, yet many are implicated in naturally occurring cancers that arise at high frequency in virus-infected animals. It is now clear that the oncogenic properties of these viruses can be attributed to the stochastic activation of cellular oncogenes by the insertion of proviral DNA. Specific cancers ensue from particular combinations of virus and target gene, and surveys of tumors of similar etiology reveal common sites of proviral integration. Some of these sites turn out to be known protooncogenes, some represent new oncogenes, whereas in others the affected gene has yet to be identified. From the established precedents, it is almost certain that each new common insertion site will reflect proximity to a candidate oncogene. The ability to vary experimentally the genetics of both the virus and the host, to alter the target cell specificity via the timing of viral infection, and to examine sequential events in doubly infected or transgenic animals holds considerable promise for unraveling the complexities of multistep carcinogenesis. The purpose of this short review is to collate the growing list of genes and loci that have been identified as sites of retroviral integration in tumors and tumor cell lines.