title: WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk wilms tumors treated with surgery alone: a children's oncology group study.
abstract: OBJECTIVE
  Children's Oncology Group defines very low-risk Wilms tumors (VLRWT) as stage I favorable histology Wilms tumors weighing less than 550 g in children younger than 24 months of age. VLRWTs may be treated with nephrectomy alone. However, 10% to 15% of VLRWTs relapse without chemotherapy. Previous studies suggest that VLRWTs with low WT1 expression and/or 11p15 loss of heterozygosity (LOH) may have increased risk of relapse. The current study validates these findings within prospectively identified children with VLRWT who did not receive adjuvant chemotherapy.
  
  
  METHODS
  Fifty-six VLRWTs (10 relapses) were analyzed for mutation of WT1, CTNNB1, and WTX; for 11p15 LOH using microsatellite analysis; and for H19DMR and KvDMR1 methylation.
  
  
  RESULTS
  11p15 LOH was identified in 19 (41%) of 46 evaluable VLRWTs and was significantly associated with relapse (P < .001); 16 of 19 were isodisomic for 11p15. WT1 mutation was identified in nine (20%) of 45 evaluable VLRWTs and was significantly associated with relapse (P = .004); all nine cases also had 11p15 LOH. All evaluable tumors showing LOH by microsatellite analysis also showed LOH by methylation analysis. Retention of the normal imprinting pattern was identified in 24 of 42 evaluable tumors, and none relapsed. Loss of imprinting at 11p15 was identified in one of 42 tumors.
  
  
  CONCLUSIONS
  WT1 mutation and 11p15 LOH are associated with relapse in patients with VLRWTs who do not receive chemotherapy. These may provide meaningful biomarkers to stratify patients for reduced chemotherapy in the future. VLRWTs show a different incidence of WT1 mutation and 11p15 imprinting patterns than has been reported in Wilms tumors of all ages.
authors.affiliation: Children's Memorial Hospital, 2300 Children's Plaza, Box 17, Chicago IL 60614, USA. eperlman@childrensmemorial.org
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Perlman
authors.forename: Paul E
authors.initials: PE
authors.lastname: Grundy
authors.forename: James R
authors.initials: JR
authors.lastname: Anderson
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Jennings
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Dome
authors.forename: Robert C
authors.initials: RC
authors.lastname: Shamberger
authors.forename: E Cristy
authors.initials: EC
authors.lastname: Ruteshouser
authors.forename: Vicki
authors.initials: V
authors.lastname: Huff
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D016162:Genes, Wilms Tumor; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009392:Nephrectomy; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor