Feline immunodeficiency virus integration in B-cell lymphoma identifies a candidate tumor suppressor gene on human chromosome 15q15.
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.
Beatty
Julia
J
Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow Veterinary School, Bearsden, Glasgow, Scotland.
Terry
Anne
A
MacDonald
Julie
J
Gault
Elizabeth
E
Cevario
Stan
S
O'Brien
Stephen J
SJ
Cameron
Ewan
E
Neil
James C
JC
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