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Feline Immunodeficiency Virus Integration in B-Cell Lymphoma Identifies a Candidate Tumor Suppressor Gene on Human Chromosome 15q15¹

Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow Veterinary School, Bearsden, Glasgow, Scotland G61 1QH [J. B., A. T., J. M., E. G., E. C., J. C. N.], and Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702 [S. C., S. J. O.]

Infection with immunosuppressive lentiviruses is associated with increased cancer risk,but most studies have implicated indirect mechanisms as the tumor cells generally lack integrated viral sequences.An exception wasfound in a B-cell lymphoma (Q254) where the tumor cells contained a single integrated feline immunodeficiency virus genome. Additional analysis now indicates that feline immunodeficiency virus integration in lymphoma Q254 resulted in promoter insertion and truncation of a conserved gene on feline chromosome B3, whereas the unaffected allele of the gene appeared to be transcriptionally down-regulated. The orthologous human gene (FLJ12973), is expressed ubiquitously and encodes a WD-repeat protein with structural similarity to DDB2, the small subunit of the xeroderma pigmentosum XP-E complex. Moreover, the gene is located within a region of frequent tumor-specific deletions on chromosome 15q15. These observations demonstrate the direct mutagenic potential of the lentiviruses and identify a new candidate tumor suppressor gene.

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