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Canonical WNT signalling determines lineage specificity in Wilms tumour

Oncogene volume 28, pages 1063–1075 (2009)Cite this article

Abstract

Wilms tumours (WTs) have two distinct types of histology with or without ectopic mesenchymal elements, suggesting that WTs arise from either the mesenchymal or epithelial nephrogenic lineages. Regardless of the presence or absence of CTNNB1 mutations, nuclear accumulation of β-catenin is often observed in WTs with ectopic mesenchymal elements. Here, we addressed the relationship between the WNT-signalling pathway and lineage in WTs by examining CTNNB1 and WT1 mutations, nuclear accumulation of β-catenin, tumour histology and gene expression profiles. In addition, we screened for mutations in WTX, which has been proposed to be a negative regulator of the canonical WNT-signalling pathway. Unsupervised clustering analysis identified two classes of tumours: mesenchymal lineage WNT-dependent tumours, and epithelial lineage WNT-independent tumours. In contrast to the mesenchymal lineage specificity of CTNNB1 mutations, WTX mutations were surprisingly observed in both lineages. WTX-mutant WTs with ectopic mesenchymal elements had nuclear accumulation of β-catenin, upregulation of WNT target genes and an association with CTNNB1 mutations in exon 7 or 8. However, epithelial lineage WTs with WTX mutations had no indications of active WNT signalling, suggesting that the involvement of WTX in the WNT-signalling pathway may be lineage dependent, and that WTX may have an alternative function to its role in the canonical WNT-signalling pathway.

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Acknowledgements

This study was supported by the Health Research Council of New Zealand.

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Authors and Affiliations

  1. Department of Biochemistry, Cancer Genetics Laboratory, University of Otago, Dunedin, New Zealand

    R Fukuzawa, M R Anaka, R J Weeks, I M Morison & A E Reeve

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  1. R Fukuzawa
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  2. M R Anaka
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  3. R J Weeks
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  4. I M Morison
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  5. A E Reeve
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Correspondence to R Fukuzawa.

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The authors have no conflict of interests.

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Fukuzawa, R., Anaka, M., Weeks, R. et al. Canonical WNT signalling determines lineage specificity in Wilms tumour. Oncogene 28, 1063–1075 (2009). https://doi.org/10.1038/onc.2008.455

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