IDENTIFICATION OF EVI-3, A NOVEL COMMON SITE OF RETROVIRAL INTEGRATION IN MOUSE AKXD B-CELL LYMPHOMAS

We have identified a novel common site of ecotropic viral integration called ecotropic viral integration site 3 (Evi-3) in B-cell lineage ly mphomas of the AKXD recombinant inbred strains of mice. A number of vi rally induced pre-B-, B-, myeloid, and T-cell lymphomas were screened for viral rearrangements at Evi-3; rearrangements were found in pre-B- and B-cell lymphomas but not in other hematopoietic tumors. Genetic m apping studies localized Evi-3 to mouse chromosome 18, distinct from p roto-oncogene and common viral integration loci identified previously in the mouse. Each proviral integration at Evi-3 is contained within a 200-bp region that lies inside a CpG island. All but one of the provi ruses have integrated in the same 5'-to-3' transcriptional orientation . Transcripts from Evi-3 are expressed in a developmentally regulated manner in B cells. Taken together, these data suggest that Evi-3 repre sents a novel proto-oncogene involved in mouse B-cell lymphomas.