F-MuLV can induce several different hematopoietic neoplasms including T-and B-cell lymphoma, erythroleukemia and myeloid leukemia. As one approach to studying disease pathogenesis in this system, we cloned sites of F-MuLV provirus insertion in host DNA in an F-MuLV-induced myeloid leukemia. One 2.5 kb region identified in this manner was found to contain an F-MuLV provirus in one other myeloid leukemia and three thymic lymphomas out of a total of 90 tumors examined. This result indicated that proviral insertion sites in F-MuLV-induced tumors in host DNA are not random. It is likely that provirus insertion in this common integration region, designated Fis-1, confers a growth advantage. We mapped the FIS-1 locus to mouse chromosome 7, about 26 cM distal to the locus for beta globin. Surprisingly, we found that Fis-1 mapped to the same position as Int-2, a putative oncogene involved in murine mammary carcinomas. Nevertheless, Fis-1 and Int-2 are distinct since 30 kb of DNA surrounding Fis-1 do not overlap 30 kb surrounding Int-2, and proviral insertions in Fis-1 do not induce Int-2 mRNA. This Fis-1/Int-2 region may be involved in human B cell neoplasia since the human homologue of Int-2 has been mapped to the same chromosomal band as a locus involved in B cell lymphoma, Bcl-1. We are currently using the technique of pulse-field and reverse-field electrophoresis to generate large scale restriction maps of the Fis-1/Int-2 region of mouse chromosome 7 determine how close these loci are to one another on a molecular scale and to search for an oncogene induced by proviral insertions at Fis-1.
