RESUMEN
FBXW7 (alias CDC4) is a p53-dependent tumor suppressor gene that exhibits mutations or deletions in a variety of human tumors. Mutation or deletion of the FBXW7 gene has been associated with an increase in chromosomal instability and cell cycle progression. In addition, the FBXW7 protein has been found to act as a component of the ubiquitin proteasome system and to degrade several oncogenic proteins that function in cellular growth regulatory pathways. By using a rapid breakpoint cloning procedure in a case of renal cell cancer (RCC), we found that the FBXW7 gene was disrupted by a constitutional t(3;4)(q21;q31). Subsequent analysis of the tumor tissue revealed the presence of several anomalies, including loss of the derivative chromosome 3. Upon screening of a cohort of 29 independent primary RCCs, we identified one novel pathogenic mutation, suggesting that the FBXW7 gene may also play a role in the development of sporadic RCCs. In addition, we screened a cohort of 48 unrelated familial RCC cases with unknown etiology. Except for several known or benign sequence variants such as single nucleotide polymorphisms (SNPs), no additional pathogenic variants were found. Previous mouse models have suggested that the FBXW7 gene may play a role in the predisposition to tumor development. Here we report that disruption of this gene may predispose to the development of human RCC.