<i>USP24</i> Is a Cancer-Associated Ubiquitin Hydrolase, Novel Tumor Suppressor, and Chromosome Instability Gene Deleted in Neuroblastoma

Abstract Deubiquitinating enzymes are increasingly recognized to play important roles in cancer, with many acting as oncogenes or tumor suppressors. In this study, we employed a bioinformatics approach screen for from family involved cancer and found USP24 potent predictor of poor outcomes neuroblastoma, an aggressive childhood cancer. resides region commonly deleted yet was independently associated disease. Deletion Usp24 murine model resulted degradation collapsin response mediator protein 2 (CRMP2), regulator axon growth, guidance, neuronal polarity. Cells lacking had significant increases spindle defects, chromosome missegregation, aneuploidy, phenotypes that were rescued by the restoration CRMP2. prevented aneuploidy maintaining spindle-associated CRMP2, which is required mitotic accuracy. Our findings further indicate suppressor may role pathogenesis neuroblastoma. Significance: This study identifies instability gene frequently neuroblastoma provides insight into