Role of genomic imprinting in Wilms' tumour and overgrowth disorders

✍ Scribed by Reeve, Anthony E.

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 739 KB
• Volume: 27
• Category: Article
• ISSN: 0098-1532
• DOI: 10.1002/(sici)1096-911x(199611)27:5<470::aid-mpo14>3.0.co;2-e

✦ Synopsis

Activation of the silent maternal ICF2 allele has recently been found in approximately half of Wilms'tumour (WTs) examined. This process of imprint relaxation leads to biallelic expression of ICF2 and it has been suggested that this is a key event in the onset of some WTs. Although it has previously been proposed that the 7 1 ~1 5 chromosome region contains a growth-promoting gene and a tumour suppressor gene, the simplest explanation is that increased expression of the ICF2 gene is responsible for somatic overgrowth in the BWS and predisposition to tumours. This model explains overgrowth in BWS cases with unbalanced translocations with paternal dup(l1 p), and cases with balanced maternal translocations which are physically close to the IGF2 gene. Maternal translocations are envisaged to disrupt the maternal ICF2 imprint by a mechanism similar to the position-effect variegation mechanism in Drosophila. Relaxation of IGF2 imprinting has also been detected in several patients with the BWS syndrome and a patient with gigantism and Wilms' tumour. Recent gene disruption experiments have shown that inactivation of the mouse h79 gene leads to biallelic lgf2 expression and extensive proportional overgrowth. This mouse model has parallels with the BWS and WT where it has been found that biallelic IGFZexpression is accomp,inied by an epigenetic modification of the H I 9 gene. From these data it is possible to speculate that an epigenetic modification of the H79gene may be the primary event leading to the relaxation of IGFZ imprinting.