Insertional mutagenesis: neoplasia arising from retroviral integration.

The integration of retroviral proviruses near cellular genes can profoundly affect their expression. Painstaking analysis of insertion sites from a large number of tumors has revealed a number of previously unknown proto-oncogenes, and has elucidated new mechanisms whereby known proto-oncogenes can be activated. A number of these genes have been implicated in tumors of clinical relevance. At the time of writing a great deal remains to be learned of the normal function of these genes in the cell. While it has yet to be demonstrated that retroviral insertion mechanisms play some role in naturally occurring human neoplasms, they must be considered in the context of retroviral gene therapy protocols now being contemplated.