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Sequential WT1 and CTNNB1 mutations and alterations of β-catenin localisation in intralobar nephrogenic rests and associated Wilms tumours: two case studies
  1. Ryuji Fukuzawa,
  2. Rosemary W Heathcott,
  3. Helen E More,
  4. Anthony E Reeve
  1. Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin, New Zealand
  1. Correspondence to:
    Dr Ryuji Fukuzawa
    Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, 710 Cumberland Street, PO Box 56, Dunedin, New Zealand; ryuji.fukuzawa{at}stonebow.otago.ac.nz

Abstract

Background: Intralobar nephrogenic rests (ILNRs) are precursor lesions for Wilms tumours and are associated with WT1 gene mutations. ILNR-associated Wilms tumours have a co-clustering of WT1 and β-catenin (CTNNB1) mutations and unique histological features characterised by a stromal-predominant histology.

Aim: To determine the order in which WT1 and CTNNB1 mutations occur to understand the ILNR–Wilms tumour sequence.

Methods: Of nine Wilms tumours with WT1 and CTNNB1 mutations, three ILNRs lesions in two Wilms tumours were available for analysis of WT1 and CTNNB1 mutations using microdissection. Immunohistochemistry was also performed to investigate how the mutations in β-catenin alter the localisation in Wilms tumour development.

Results:WT1 mutations were present in the ILNRs, however CTNNB1 mutations were absent. Immunohistochemistry for WT1 confirmed inactivation of WT1 in both ILNRs and Wilms tumours. Both the ILNRs and the associated Wilms tumours had similar immunostaining patterns for β-catenin in the blastemal and epithelial components. Although rhabdomyoblasts were not included in ILNRs, the associated Wilms tumours showed rhabdomyogenic differentiation with a positive β-catenin nuclear staining.

Conclusions: The results suggest that CTNNB1 mutation is a later event in Wilms tumourigenesis. CTNNB1 mutations might be associated with rhabdomyogenesis.

  • ILNR, intralobar nephrogenic rest
  • LOH, loss of heterozygosity
  • nephroblastoma
  • beta-catenin
  • Wnt sinalling pathway
  • microdissection

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Footnotes

  • Published Online First 15 December 2006

  • Funding: This work was supported by the Health Research Council of New Zealand, the Cancer Society of New Zealand, and the NZ Lottery Health Grants Board.

  • Competing interests: None.

  • Ethics approval for this study was obtained from North Health Ethics Committee, Auckland, New Zealand.

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