Frequent overexpression of cyclin D2/cyclin-dependent kinase 4 in Wilms' tumor

The expression status of the three cyclin D genes (CCND1, CCND2 and CCND3), the two cyclin D-dependent kinase genes (CDK4 and CDK6) and the p16INK4a gene was studied in a series of 47 Wilms' tumors, 16 normal mature kidneys and two fetal kidneys. We showed predominant overexpression of CCND2 and CDK4 compared to CCND1/D3 and CDK6 respectively. We found a specific correlation between relapse and CDK4 overexpression, but not CDK6 overexpression. We did not identify any methylation of the p16INK4a promoter. This suggests that dysregulation of CCND2 and CDK4 plays a specific role in WT tumorigenesis.