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-1. Gfi-1 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-1, and Southern analysis showed that Gfi-1, like Evi-5, is a common integration site in AKXD T-cell tumors. With one exception, Evi-5 and Gfi-1 integrations were mutually exclusive. Ten of the tumors with Evi-5 or Gfi-1 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-1 is causally associated with this disease process.
D000818:Animals; D015139:Blotting, Southern; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015698:Genomic Library; D016399:Lymphoma, T-Cell / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D005810:Multigene Family; D011995:Recombination, Genetic; D015183:Restriction Mapping; D012190:Retroviridae / Q000235:genetics*; D016662:Virus Integration
D004247:DNA