Methylation of the RASSF1A promoter is predictive of poor outcome among patients with Wilms tumor

Background Wilms tumor (WT) has a survival rate of 90% following multimodality therapy. Nevertheless, there are some groups of patients with event-free survival rates less than 75%. In addition to clinical prognostic factors, loss of heterozygosity at 1p and/or 16q has been used to determine treatment intensity. However, the incidence of this abnormality is low, and new biomarkers are still needed. Procedure We analyzed methylation status of three tumor suppressor genes; Ras-association domain family 1 protein, isoform A (RASSF1A), DCR2, and CASP8, in 84 WTs using conventional methylation-specific PCR (cMSP), and the results were correlated with outcome. Furthermore, we analyzed the methylation status of RASSF1A by quantitative MSP (qMSP) in 171 WTs, and evaluated clinical and genetic differences between the methylated and unmethylated tumors. Results RASSF1A was the most frequently methylated gene identified by cMSP, and associated with a poor outcome. Patients with a RASSF1A-methylated tumor had shorter overall and event-free survival periods (P = 0.043 and 0.018, respectively), when a cut-off value of 7% by qMSP was used. The methylation was more frequent in tumors of older children than younger children (P