The fit-1 common integration locus in human and mouse is closely linked toMYB

The fit-1 locus was originally identified as a common insertion site fur fe line leukemia virus (FeLV) in thymic lymphosarcomas induced by FeLV-myc rec ombinant viruses, suggesting that it harbors a gene that cooperates with My c in T-cell leukemogenesis. We have previously mapped the fit-1 locus to fe line Chromosome (Chr) B2. We have now identified conserved sequences that a llow the mapping of the murine homolog using the European Interspecific Bac kcross (EUCIB). This shows that fit-1 is located on mouse Chr 10, 1cM proxi mal to Ahi-1, a murine retroviral integration locus that is closely linked to Myb. Moreover, the physical linkage to MYB is maintained in the human ge nome, as shown by cloning of the human homolog fit-1 from a Chr 6 cosmid li brary and a series of overlapping PAC clones. Generation of a contig map ar ound the human homolog of fit-1 reveals that it is approximately 100-kb ups tream of MYB. In addition to fit-1 and Ahi-1, two other common insertion si tes, Mis-2 and Mml-1, have also been mapped adjacent to Myb on mouse Chr 10 . Previous analysis of tumors carrying insertions at fit-1, Mml-1, Mis-2 an d Ahi-1 showed no obvious abnormalities in Mb expression. However, the clus ter of viral insertion loci in this region suggests either the presence of a closely linked activation target or that subtle effects on Myb, have been overlooked.