Oncogenes: clinical relevance.

The last 10 years have seen something of a revolution in experimental carcinogenesis, sparked by the discovery of oncogenes [1-3]. The first such gene and most of the ones that followed [1] have been isolated as part of the genome of a tumor-inducing retrovirus. Mostly obtained from birds and mice, these viral oncogenes are nearly identical to genes present in normal cells and, because of their high degree of evolutionary conservation, could be used directly to isolate their human counterparts. What implicated these genes in chemically induced and natural tumors? First indications came from oncogene transduction experiments with retroviruses and chemically transformed mouse and rat cells [4--6]. The transduction experiments led to the isolation of new oncogene-carrying viruses [5, 7, 8], but proof of the supposition that cellular oncogenes were involved in chemical carcinogenesis came from another quarter. Gene transfer methods using transfection of chromosomal DNA had become more efficient [9,10], and their application to the search for transforming genes in chemically transformed mouse cells was successful [11]. The advent of molecular cloning greatly accelerated the identification of transfected, focusinducing DNA, thus leading to the following central findings. DNA from transformed cells was active, while DNA from untransformed cells had very little or no activity. The transforming DNA was related to one of several groups of