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
✍ Scribed by Barbara Simon-Kayser; Catherine Scoul; Karine Renaudin; Pascal Jezequel; Olivier Bouchot; Jérôme Rigaud; Stéphane Bezieau
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 533 KB
- Volume
- 43
- Category
- Article
- ISSN
- 1045-2257
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✦ Synopsis
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.