Spindle Assembly Checkpoint Gene Expression in Childhood Adrenocortical Tumors (ACT): Overexpression of Aurora Kinases A and B Is Associated With a Poor Prognosis

BackgroundPediatric adrenocortical tumors (ACT) are rare malignancies and treatment has a small impact on survival in advanced disease and the discovery of potential target genes could be important in new therapeutic approaches.MethodsThe mRNA expression levels of spindle checkpoint genes AURKA, AURKB, BUB, and BUBR1 were analyzed in 60 children with ACT by quantitative real time PCR. the anticancer effect of ZM447439, an experimental AURK inhibitor, was analyzed in a primary childhood ACT culture carrying the TP53 p.R337H mutation.ResultsA significant association was observed between malignancy as defined by Weiss score 3 and higher AURKA (2.0-fold, P=0.01), AURKB (7.0-fold, P=0.007), and BUBR1 (5.8-fold, P=0.007) gene expression, and between unfavorable event (death or relapse) and higher expression of AURKA (6.0-fold, P=0.034) and AURKB (17-fold, P=0.013). Overexpression of AURKA and AURKB was associated with lower event-free survival in uni- (P