title: Feline immunodeficiency virus integration in B-cell lymphoma identifies a candidate tumor suppressor gene on human chromosome 15q15.
abstract: 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.
authors.affiliation: Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow Veterinary School, Bearsden, Glasgow, Scotland.
authors.forename: Julia
authors.initials: J
authors.lastname: Beatty
authors.forename: Anne
authors.initials: A
authors.lastname: Terry
authors.forename: Julie
authors.initials: J
authors.lastname: MacDonald
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gault
authors.forename: Stan
authors.initials: S
authors.lastname: Cevario
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Ewan
authors.initials: E
authors.lastname: Cameron
authors.forename: James C
authors.initials: JC
authors.lastname: Neil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002415:Cats; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D016679:Genome, Viral; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000235:genetics*; D016180:Lentivirus Infections / Q000150:complications / Q000235:genetics / Q000662:veterinary / Q000821:virology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000662:veterinary / Q000821:virology*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015533:Transcriptional Activation; D016662:Virus Integration