Epigenotyping as a tool for the prediction of tumor risk and tumor type in patients with Beckwith-Wiedemann syndrome (BWS).

Objectives: Patients with Beckwith-Wiedemann syndrome (BWS) have a risk of 7.5% to 10% of developing childhood tumors, 60% of which are Wilms' tumors. Aberrant methylation of two distinct clusters of imprinted genes on chromosome 11p15 is detected in approximately 70% of BWS cases. Our aim was to determine associations between the imprinting status of both imprinting clusters (BWSIC1/2) and the tumor incidence and type.

Study Design: Methylation patterns of H19 and KCNQ1OT1 were collected in 114 patients with BWS with a clinical diagnosis. The patients were followed until 5 years of age, and tumor incidence and type were registered.

Results: A lower risk of developing childhood tumors was found among patients with a methylation defect limited to BWSIC2 compared with other patients with BWS. No Wilms' tumors were found in this group, whereas in patients with a methylation defect limited to BWSIC1 Wilms' tumor was the most common tumor.

Conclusions: In addition to clinical factors indicative for a high tumor risk (hemihypertrophy, nephromegaly), methylation patterns discriminate between patients with BWS with a high and low tumor risk. It also is possible to predict whether they are at risk of developing a Wilms' tumor. Epigenotyping of patients is important to select the type of screening protocol to be proposed to these patients.