EVI-5, A COMMON SITE OF RETROVIRAL INTEGRATION IN AKXD T-CELL LYMPHOMAS, MAPS NEAR GFI-1 ON MOUSE CHROMOSOME-5

We have identified a novel common site of retroviral integration, Evi-5, in AKXD T-cell lymphomas, All proviruses located at Evi-5 are clustered within a 7-kb genomic region and, where determined, are oriented in the same transcriptional direction. Interspecific backcross analysis localized Evi-5 to mouse chromosome 5, where it cosegregated with another common viral integration site, Gfi-l. Gfi-l encodes a novel zinc finger transcription factor whose expression is thought to be important for interleukin-2 signaling. Physical mapping studies showed that Evi-5 is located approximately 18 kb upstream of Gfi-l, and Southern analysis showed that Gfi-l, like Evi-5, is a common integration site in AKXD T-cell tumors. With one exception, Evi-5 and Gfi-l integrations were mutually exclusive, Ten of the tumors with Evi-5 or Gfi-l integrations also harbored viral integrations at other common integration sites causally associated with T-cell disease, These results are consistent with the hypothesis that T-cell lymphomagenesis is a multistep disease and that viral integration at Evi-5 or Gfi-l is causally associated with this disease process.