title: Wilms' tumor in patients with 9q22.3 microdeletion syndrome suggests a role for PTCH1 in nephroblastomas.
abstract: Nephroblastoma (Wilms' tumor; WT) is the most common renal tumor of childhood. To date, several genetic abnormalities predisposing to WT have been identified in rare overgrowth syndromes. Among them, abnormal methylation of the 11p15 region, GPC3 and DIS3L2 mutations, which are responsible for Beckwith-Wiedemann, Simpson-Golabi-Behmel and Perlman syndromes, respectively. However, the underlying cause of WT remains unknown in the majority of cases. We report three unrelated patients who presented with WT in addition to a constitutional 9q22.3 microdeletion and dysmorphic/overgrowth syndrome. 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 array comparative genomic hybridization method, we analyzed the DNA extracted from the blood samples of nine patients with overgrowth syndrome and WT, but did not identify any deleterious chromosomal imbalances in these patients. These findings strongly suggest that patients with constitutional 9q22.3 microdeletion have an increased risk of WT, and that PTCH1 have a role in the pathogenesis of nephroblastomas.
authors.affiliation: Service de Génétique Médicale, CHU Nantes, Nantes, France. bertrand.isidor@chu-nantes.fr
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
authors.forename: Delfine
authors.initials: D
authors.lastname: Lafon
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Plessis
authors.forename: Elodie
authors.initials: E
authors.lastname: Lacaze
authors.forename: Caroline
authors.initials: C
authors.lastname: Kannengiesser
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rossignol
authors.forename: Olivier
authors.initials: O
authors.lastname: Pichon
authors.forename: Annaig
authors.initials: A
authors.lastname: Briand
authors.forename: Dominique
authors.initials: D
authors.lastname: Martin-Coignard
authors.forename: Maria
authors.initials: M
authors.lastname: Piccione
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Cécile
authors.initials: C
authors.lastname: Jeanpierre
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sévenet
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D005320:Fetal Macrosomia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface