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

6533b873fe1ef96bd12d593f

RESEARCH PRODUCT

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

Franck Bourdeaut Nicolas Sevenet Dominique Martin-coignard Maria Piccione Sylvie Rossignol Elodie Lacaze Bertrand Isidor Caroline Kannengiesser Annaig Briand Cédric Le Caignec Cécile Jeanpierre Delfine Lafon Ghislaine Plessis Olivier Pichon Olivier Delattre Albert David

subject

Adult Patched Receptors medicine.medical_specialty Pathology PTCH1 Adolescent Nonsense mutation CNV Short Report Receptors Cell Surface Biology medicine.disease_cause Wilms’ tumor Wilms Tumor Fetal Macrosomia Settore MED/38 - Pediatria Generale E Specialistica Pregnancy Internal medicine Genetics medicine Humans Perlman syndrome Child overgrowth Genetics (clinical)Mutation Comparative Genomic Hybridization Wilms' tumor PTCH1 Gene Microdeletion syndrome FANCC nephroblastoma medicine.disease Kidney Neoplasms Patched-1 Receptor Endocrinology PTCH1 Settore MED/03 - Genetica Medica Overgrowth syndrome Mutation Female Chromosome Deletion Chromosomes Human Pair 9 Comparative genomic hybridization

description

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.

year	journal	country	edition	language
2012-11-21

10.1038/ejhg.2012.252 https://europepmc.org/articles/PMC3722950/