The role of promoter insertion in the induction of neoplasia.

It has been shown in several retroviral systems that proviral DNA can integrate into the host genome in such a manner that expression of a nearby oncogene is enhanced. This enhancement results from either a direct promotion of transcription from a strong promoter within the proviral 3' LTR or from less well defined activation in which sequences known as 'enhancers' mediate an increase in the transcription of nearby genes. As a result of this observation, potential oncogenes can now be found by identifying genes whose activity is modulated by the nearby insertion of transcriptional activating elements during oncogenesis. It has also been shown that the genome of a retroviral-like IAP can similarly become integrated adjacent to an oncogene and produce an increase in transcription of that gene. Other examples of possible nonviral promoter insertion events that take place in the oncogenesis of the human Burkitt's lymphoma are discussed elsewhere in this volume.