Mechanism of Tumor Formation in Familial Beckwith-Wiedemann Syndrome

Background

Beckwith-Wiedemann syndrome (BWS) is a childhood cancer predisposition disorder that is caused by genetic and epigenetic changes on chromosome 11. Most cases of BWS are not hereditary, especially those with an epigenetic alteration. However, rare familial cases of inherited epigenetic changes do exist, and can provide insight into the mechanism underlying the epigenetic changes that lead to BWS and subsequent tumor formation in these patients. As part of our BWS registry, we have identified and obtained samples from a large family with a heritable form of BWS. Their BWS is caused by complete loss of methylation on one region of chromosome 11.

Normally, methylation is erased and reset during fertilization. Because affected members in this family have total loss of methylation, their BWS must be due to a genetic change that acts on either the establishment or maintenance of methylation. Understanding the genetics behind the epigenetic alteration seen in this family will provide insight into how the epigenetic changes in BWS come about, and why they cause cancer.

Project Goal

Using methylation and genome-wide analysis, we propose to investigate the cause of BWS and tumor risk of this family.