title: Molecular evidence of the independent origin of multiple Wilms tumors in a case of WAGR syndrome.
abstract: BACKGROUND
  This study investigated the genetic events leading to tumorigenesis in a patient affected with WAGR syndrome who developed multiple distinct Wilms tumors (WTs).
  
  
  RESULTS
  At 1 year of age, the child developed two synchronous bilateral WTs that were resected by partial nephrectomy. Histologically, these tumors were fetal rhabdomyomatous nephroblastomas. Immunohistochemical study revealed the absence of nuclear expression of WT1 protein, while beta-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular investigations of WT1 gene and exon 3 of beta-catenin (CTNNB1) gene detected no mutations. At 4 years of age, 28 months after the chemotherapy completion, a third WT was diagnosed in the left kidney, and surgically removed before any further chemotherapy. Nine months after surgery, a metastasis was detected in the left lung. Both the third renal tumor and the lung metastasis showed a blastema-predominant morphology. Immunohistochemistry confirmed the lack of expression of WT1 protein, while beta-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular analysis of the third renal tumor and the lung metastasis revealed a 4 bp deletion in exon 7 of WT1 gene, leading to a frameshift of the reading frame and to a premature stop of the translation (c.925_928delACTC, p.T309LfsX71); no mutations in the exon 3 of the beta-catenin gene were documented.
  
  
  CONCLUSIONS
  These data demonstrate that multiple WTs can arise as a consequence of different genetic events in a patient with genetic predisposition, such as WAGR syndrome.
authors.affiliation: Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Uccini
authors.forename: Daniela
authors.initials: D
authors.lastname: Perotti
authors.forename: Cristina
authors.initials: C
authors.lastname: Colarossi
authors.forename: Antonella
authors.initials: A
authors.lastname: Stoppacciaro
authors.forename: Michele
authors.initials: M
authors.lastname: Sardella
authors.forename: Olga
authors.initials: O
authors.lastname: Mannarino
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.forename: Paola
authors.initials: P
authors.lastname: Casieri
authors.forename: Denis
authors.initials: D
authors.lastname: Cozzi
authors.forename: Loredana
authors.initials: L
authors.lastname: Amoroso
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Carlo
authors.initials: C
authors.lastname: Dominici
mesh_terms: D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms; D008297:Male; D017624:WAGR Syndrome / Q000235:genetics*; D025721:WT1 Proteins / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics
chemical_list: D025721:WT1 Proteins; D051176:beta Catenin