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

• Published in: The Journal of pediatrics Vol. 145; no. 6; pp. 796 - 799
• Main Authors: Bliek, Jet, Gicquel, Christine, Maas, Saskia, Gaston, Véronique, le Bouc, Yves, Mannens, Marcel
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-12-2004; Elsevier
• Subjects: Beckwith-Wiedemann Syndrome - complications; Beckwith-Wiedemann Syndrome - genetics; Biological and medical sciences; Child, Preschool; France - epidemiology; General aspects; Genes, Wilms Tumor; Genotype; Humans; Incidence; Kidney Neoplasms - etiology; Kidney Neoplasms - genetics; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - isolation & purification; Methylation; Neoplasms - classification; Neoplasms - epidemiology; Netherlands - epidemiology; Potassium Channels, Voltage-Gated - genetics; Potassium Channels, Voltage-Gated - isolation & purification; Predictive Value of Tests; Risk Factors; Wilms Tumor - etiology; Wilms Tumor - genetics; France; Netherlands; UPD; BWS; Human; Pediatrics; Beckwith Wiedemann syndrome; Prediction; Patient; Risk; Congenital disease; Genetic disease; Type; Abdominal disease; Risk factor; Tumor; Predictive factor
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2004.08.007

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 ∼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.
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.
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.
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.