Provirus tagging as an instrument to identify oncogenes and to establish synergism between oncogenes

Insertional mutagenesis is one of the mechanisms by which retroviruses can transform cells. Once a provirus was found in the vicinity of c-myc, with the concomitant activation of this gene, other proto-oncogenes were shown to be activated by proviral insertion in retrovirally-induced tumors. Subsequently, cloning of common proviral insertion sites led to the discovery of a series of new (putative) oncogenes. Some of these genes have been shown to fulfill key roles in growth and development. In this review I shall describe how proviruses can be used to identify proto-oncogenes, and list the loci, identified by this method. Furthermore, I shall illuminate the potential of provirus tagging by showing that it not only can mark new oncogenes, but can also be instrumental in defining sets of (onco)genes that guide a normal cell in a step-by-step fashion to its fully transformed, metatasizing, counterpart.