EPIGENETIC LESIONS AT THE H19 LOCUS IN WILMS-TUMOR PATIENTS

To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms' tumours (WTs). I n most WTs (18/25), H19 RNA was reduced at least 20-fold from fetal ki dney levels. Of the expression-negative tumours ten retained 11p15.5 h eterozygosity: in nine of these, H19 DNA was biallelically hypermethyl ated and in two cases hypermethylation locally restricted to H19 seque nces was also present in the non-neoplastic kidney parenchyma. IGF2 mR NA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactiv ation of H19 in Wilms' tumorigenesis.