<i>Sint1</i> , a Common Integration Site in SL3-3-Induced T-Cell Lymphomas, Harbors a Putative Proto-Oncogene with Homology to the Septin Gene Family

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  • Annette Balle Sørensen
    <!--label omitted: 1-->Department of Molecular and Structural Biology1 and
  • Anders H. Lund
    <!--label omitted: 1-->Department of Molecular and Structural Biology1 and
  • Steen Ethelberg
    <!--label omitted: 1-->Department of Molecular and Structural Biology1 and
  • Neal G. Copeland
    <!--label omitted: 2-->Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 217022
  • Nancy A. Jenkins
    <!--label omitted: 2-->Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 217022
  • Finn Skou Pedersen
    <!--label omitted: 1-->Department of Molecular and Structural Biology1 and

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<jats:title>ABSTRACT</jats:title> <jats:p> 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 ( <jats:italic>Sint1</jats:italic> ), 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, <jats:italic>Pad3</jats:italic> . Two overlapping genomic λ 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 <jats:italic>Sint1</jats:italic> . 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. </jats:p>

Journal

  • Journal of Virology

    Journal of Virology 74 (5), 2161-2168, 2000-03

    American Society for Microbiology

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