FLVI-2, A TARGET OF RETROVIRAL INSERTIONAL MUTAGENESIS IN FELINE THYMIC LYMPHOSARCOMAS, ENCODES BMI-1

LC-FeLV is a myc-containing strain of feline leukemia virus which indu ces thymic lymphosarcoma in the domestic cat with short latency. A loc us in feline DNA, termed flvi-2, is commonly interrupted in naturally occurring and experimentally induced thymic lymphosarcomas containing LC-FeLV; thus, interruption of a gene encoded by flvi-2 may cooperate with the myc oncogene in the induction of T-cell tumors by LC-FeLV. Cl ones homologous to flvi-2 have been isolated from a normal human thymu s cDNA library. Nucleotide sequence analysis of the cDNA clones demons trates that flvi-2 encodes bmi-1, a gene previously identified as a ta rget for MoMuLV integration and as a myc-collaborator in retrovirally- induced B-cell lymphomas in Emu-myc transgenic mice. In feline thymic lymphomas, retroviral integrations occur downstream of the gene, and r esult in enhanced expression of a bmi-1 transcript of normal size. The se findings demonstrate the interruption of bmi-1 in natural as well a s experimentally induced tumors, implicate the activation of bmi-1 in the induction of T-cell as well as B-cell lymphoma, and support the pr emise that bmi-1 functions as a myc collaborator.