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.
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.
Authors: F R Grati; L Turolla; P D'Ajello; A Ruggeri; M Miozzo; G Bracalente; D Baldo; L Laurino; R Boldorini; E Frate; N Surico; L Larizza; F Maggi; G Simoni Journal: J Med Genet Date: 2007-01-26 Impact factor: 6.318
Authors: Vir B Singh; Sirinapa Sribenja; Kayla E Wilson; Kristopher M Attwood; Joanna C Hillman; Shilpa Pathak; Michael J Higgins Journal: Development Date: 2017-04-20 Impact factor: 6.868
Authors: Jochen K Lennerz; Robert J Timmerman; Dorothy K Grange; Michael R DeBaun; Andrew P Feinberg; Barbara A Zehnbauer Journal: J Mol Diagn Date: 2010-07-08 Impact factor: 5.568
Authors: R H Scott; L Walker; Ø E Olsen; G Levitt; I Kenney; E Maher; C M Owens; K Pritchard-Jones; A Craft; N Rahman Journal: Arch Dis Child Date: 2006-07-20 Impact factor: 3.791