Wilms’ tumor in patients with 9q22.3 microdeletion syndrome suggests a role for PTCH1 in nephroblastomas

Nephroblastoma (Wilms’ tumor; WT) is the most common renal tumor of childhood. To date, several genetic abnormalitiespredisposing to WT have been identified in rare overgrowth syndromes. Among them, abnormal methylation of the 11p15region, GPC3 and DIS3L2 mutations, which are responsible for Beckwith–Wiedemann, Simpson–Golabi–Behmel and Perlmansyndromes, respectively. However, the underlying cause of WT remains unknown in the majority of cases. We report threeunrelated patients who presented with WT in addition to a constitutional 9q22.3 microdeletion and dysmorphic/overgrowthsyndrome. The size of the deletions was variable (ie, from 1.7 to 8.9 Mb) but invariably encompassed the PTCH1 gene.Subsequently, we identified a somatic PTCH1 nonsense mutation in the renal tumor of one patient. In addition, by arraycomparative genomic hybridization method, we analyzed the DNA extracted from the blood samples of nine patients withovergrowth syndrome and WT, but did not identify any deleterious chromosomal imbalances in these patients. These findingsstrongly suggest that patients with constitutional 9q22.3 microdeletion have an increased risk of WT, and that PTCH1 have arole in the pathogenesis of nephroblastomas.