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


METHODS
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.
Bliek
Jet
J
Departments of Clinical Genetics and Anatomy & Embryology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. j.bliek@amc.uva.nl
Gicquel
Christine
C
Maas
Saskia
S
Gaston
Véronique
V
Le Bouc
Yves
Y
Mannens
Marcel
M
D001506:Beckwith-Wiedemann Syndrome / Q000150:complications / Q000235:genetics*; D002675:Child, Preschool; D005602:France / Q000453:epidemiology; D016162:Genes, Wilms Tumor; D005838:Genotype; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000209:etiology / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics* / Q000302:isolation & purification; D008745:Methylation; D009369:Neoplasms / Q000145:classification / Q000453:epidemiology*; D009426:Netherlands / Q000453:epidemiology; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000302:isolation & purification; D011237:Predictive Value of Tests; D012307:Risk Factors; D009396:Wilms Tumor / Q000209:etiology / Q000235:genetics*
C485621:KCNQ1OT1 long non-coding RNA, human; D008565:Membrane Proteins; D024642:Potassium Channels, Voltage-Gated