title: Molecular cloning and characterization of FBXO47, a novel gene containing an F-box domain, located in the 17q12 band deleted in papillary renal cell carcinoma.
abstract: Genetic alterations of chromosome arm 17q occur in numerous tumor types, including breast and ovarian tumors, suggesting the presence of a tumor-suppressor gene on the long arm of chromosome 17 that is critical for carcinogenesis. Previous studies have shown an allelic imbalance (70% gain or loss) of 17q in papillary renal cell carcinoma (pRCC). In this study, we analyzed 15 cases of pRCC for loss of heterozygosity with the use of 7 microsatellite markers between 17q11 and 17q23. We identified a minimal deleted region in which the D17S250 marker (17q12) was deleted in 50% (7 of 14) of informative cases. We isolated the cDNA of a novel gene named FBXO47, which is near D17S250. Human FBXO47 is composed of 11 exons and spans approximately 30 kb of genomic DNA. FBXO47 cDNA consists of 2,269 bp with a 1,359-bp open-reading frame. Of note is that FBXO47 is preferentially expressed in normal tissue relative to the corresponding tumor tissue, particularly in the kidney, liver, and pancreas and to a lesser extent in the thyroid gland, stomach, and small intestine. The putative protein encoded by this gene is made up of 453 amino acids and belongs to the F-box family, most of whose members, such as SKP2 and FBW7, have been implicated in carcinogenesis. Together, these results indicate that FBX047 has a potential role as a tumor-suppressor gene.
authors.affiliation: Laboratoire d'Etude du Polymorphisme de l' ADN, Faculté de Médecine, Nantes, France. bsimon@sante.univ-nantes.fr
authors.forename: Barbara
authors.initials: B
authors.lastname: Simon-Kayser
authors.forename: Catherine
authors.initials: C
authors.lastname: Scoul
authors.forename: Karine
authors.initials: K
authors.lastname: Renaudin
authors.forename: Pascal
authors.initials: P
authors.lastname: Jezequel
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouchot
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rigaud
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bezieau
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D016384:Consensus Sequence; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D051858:Forkhead Transcription Factors; D017353:Gene Deletion; D006801:Humans; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; C500586:FBXO47 protein, human; C478770:FOXO6 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors