Sint1, a common integration site in SL3-3-induced T-cell lymphomas, harbors a putative proto-oncogene with homology to the septin gene family

The murine retrovirus SL3-3 is a potent inducer of T-cell lymphomas when in oculated into susceptible newborn mice. Previously, DNAs from twenty SL3-3- induced tumors were screened by PCR for provirus integration sites. Two out of 20 tumors demonstrated clonal provirus insertion into a common region. This region has now been isolated and characterized. The region, named SL3- 3 integration site 1 (Sint1), maps to the distal end of mouse chromosome 11 , corresponding to human chromosome 17q25, and may be identical to a mouse mammary tumor virus integration site in a T-cell lymphoma, Pad3. Two overla pping genomic lambda clones spanning about 35 kb were isolated and used as a starting point for a search for genes in the neighborhood of the virus in tegration sites. A genomic fragment was used as a hybridization probe to is olate a 3-kb cDNA clone, the expression of which was upregulated in one of two tumors harboring a provirus in Sint1, The cDNA clone is predicted to en code a protein which shows 97.0% identity to a human septin-like protein en coded by a gene which has been found as a fusion partner gene of MLL in an acute myeloid leukemia with a t(11;17)(q23;q25). Together these findings ra ise the possibility that a proto-oncogene belonging to the septin family, a nd located about 15 kb upstream of the provirus integration sites, is invol ved in murine leukemia virus-induced T-cell lymphomagenesis.