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.
Copyright 2005 Wiley-Liss, Inc.