Figure 2.

Mechanisms of insertional mutagenesis.

Schematic representation of two copies of a provirus integrated upstream the regulatory regions and between exons 1 and 2 of a proto-oncogene. The full-length LTRs in the provirus are represented by black boxes L; P represents the promoter region of the gene; the numbered boxes represent the exons; the arrows represent the orientation of transcription. A) as reported in some of the patients of the SCID-X1 trials, the enhancer elements of the LTR can activate the expression of the proto-oncogene or B) as reported by Bokhoven et al in vitro,80 fusion transcripts of viral RNA and cellular RNA are generated due to aberrant splicing between the splicing donor site downstream of the 5′ LTR and a splicing acceptor site upstream of exon 2 of the proto-oncogene.