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

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 FBX047, which is near D17S250. Human FBX047 is composed of 11 exons and spans approximately 30 kb of genomic DNA. FBX047 cDNA consists of 2,269 bp with a 1,359-bp open-reading frame, Of note is that FBX047 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. (c) 2005 Wiley-Liss, Inc.