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 inoculated 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 overlapping 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 integration sites. A genomic fragment was used as a hybridization probe to isolate 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 encode a protein which shows 97.0% identity to a human septin-like protein encoded 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 raise the possibility that a proto-oncogene belonging to the septin family, and located about 15 kb upstream of the provirus integration sites, is involved in murine leukemia virus-induced T-cell lymphomagenesis.
Sørensen
A B
AB
Department of Molecular and Structural Biology, University of Aarhus, DK-8000 Aarhus C, Denmark.
Lund
A H
AH
Ethelberg
S
S
Copeland
N G
NG
Jenkins
N A
NA
Pedersen
F S
FS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D005813:Genes, Synthetic; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics; D011533:Proviruses / Q000235:genetics*; D012334:RNA, Neoplasm / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D012192:Retroviridae Infections / Q000209:etiology*; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000209:etiology*; D016662:Virus Integration
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; C116974:sint1 protein, synthetic