title: Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the cadherin-associated protein beta1 gene CTNNB1 for patients with Wilms tumors: results of long-term surveillance of 71 patients from International Society of Pediatric Oncology Study 9/Society for Pediatric Oncology.
abstract: BACKGROUND
  Mutations in the Wilms tumor (WT) suppressor 1 gene (WT1) and the cadherin-associated protein beta1 gene (CTNNB1) are found predominantly in stromal type WT, defining a genetic subgroup. The clinical relevance of these mutations remains to be determined.
  
  
  METHODS
  A long-term follow-up study was performed for 71 patients (International Society of Pediatric Oncology Study 9/Society for Pediatric Oncology; n = 77 tumors) with known molecular genetic status. Eight patients had bilateral disease, including 2 patients with a WT in both kidneys and 5 patients with a WT in 1 kidney and nephrogenic rests (NRs) in the other kidney. The response to preoperative chemotherapy, relapses, metastases, metachronous tumor development, and deaths were evaluated with a median follow-up of 12 years and 4 months.
  
  
  RESULTS
  Nineteen patients (n = 24 tumors) had WT1 mutations, and 16 were constitutional mutations. Three patients with germline mutations had second tumor events: Two patients developed a WT in the kidney with NRs 3 years and 11 years after the first tumor; and 1 patient developed second tumors after 2 years, 1 in the kidney with a previous WT and 1 in the kidney with a previous NR. Eighteen of the WT1 mutant tumors were analyzed for CTNNB1 mutations, and all had mutations. A poor volumetric response (progression and <50% reduction) was observed in all patients who had tumors with a WT1 mutation and in 23 of 52 nonmutant tumors.
  
  
  CONCLUSIONS
  Patients with WT1 germline mutations had an increased risk for bilateral disease and second tumor events. Therefore, the authors concluded that tumor surveillance until adulthood should be considered. Although tumors with both WT1 and CTNNB1 mutations had a poor volumetric response, there was no significant difference in overall survival in this cohort of patients with and without WT1 mutations.
authors.affiliation: Institute of Human Genetics and Anthropology, Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany. royer@uni-duesseldorf.de
authors.forename: Brigitte
authors.initials: B
authors.lastname: Royer-Pokora
authors.forename: Angela
authors.initials: A
authors.lastname: Weirich
authors.forename: Valerie
authors.initials: V
authors.lastname: Schumacher
authors.forename: Constanze
authors.initials: C
authors.lastname: Uschkereit
authors.forename: Manfred
authors.initials: M
authors.lastname: Beier
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.forename: Frank
authors.initials: F
authors.lastname: Autschbach
authors.forename: Dominique
authors.initials: D
authors.lastname: Schneider
authors.forename: Melissa
authors.initials: M
authors.lastname: von Harrach
mesh_terms: D005500:Follow-Up Studies; D016162:Genes, Wilms Tumor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000401:mortality; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin