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  • Original Paper
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Changes in WT1 splicing are associated with a specific gene expression profile in Wilms' tumour

Oncogene volume 21, pages 5566–5573 (2002)Cite this article

Abstract

Wilms' tumour (WT) or nephroblastoma is the most frequent kidney cancer in children. In a previous study, we reported alterations to WT1 transcription in 90% of WT tested, with decreased exon 5 +/− isoform ratio being the most frequent alteration (56% of WT). We now report an approach based on cDNA profiling of tumour pools to identify genes likely to be dysregulated in association with a decreased WT1 exon 5 +/− ratio. We compared the expression profiles of pools of tumours classified according to whether this isoform imbalance was present (five tumours) or not (four tumours), using Atlas Cancer cDNA expression arrays. Fourteen of 588 genes tested displayed specific up-regulation (CCND2, PCNA, N-MYC, E2F3, TOP2A, PAK1, DCC and PCDH2) or down-regulation (VEGF, IGFBP5, TIMP3, ARHB, C-FOS and CD9) in the pool of tumours with decreased exon 5 +/− ratio. These results were validated by RT–PCR analysis of four genes (CCND2, PCNA, VEGF and IGFBP5). We extended the analysis of VEGF expression to 51 tumours by real-time RT–PCR and ascertained differential expression of this gene associated with WT1 expression pattern. Moreover, our results suggest that the VEGF expression level may be of prognosis relevance for relapsed patients.

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Acknowledgements

We thank Drs P Boute, M Fabre, J-C Fournet, B Gilbert, F Jaubert, F Pein, B Pautard and H van Tinteren for providing tumour samples and clinical data. This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Association pour la Recherche sur le Cancer and the Ligue Nationale contre le Cancer. D Baudry was supported by grants from the Association pour la Recherche sur le Cancer and from the Fondation pour la Recherche Médicale and M Faussillon was supported by a grant from the Ministère de la Recherche et de la Technologie.

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Author notes

  1. Muriel Rigolet

    Present address: UMR 7592 CNRS, Institut Jacques Monod, Paris, Cedex 05, 75251, France

Authors and Affiliations

  1. INSERM U383, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, Cedex 15, 75743, France

    Dominique Baudry, Marine Faussillon, Marie-Odile Cabanis, Muriel Rigolet, Claudine Junien & Cécile Jeanpierre

  2. Institut Curie, Paris, 75248, France

    Jean-Michel Zucker

  3. Institut Gustave Roussy, Villejuif, 94805, France

    Catherine Patte

  4. Clinique Chirurgicale infantile, Hôpital Necker-Enfants Malades, Paris, Cedex 15, 75743, France

    Sabine Sarnacki

  5. Service d'Anatomie Pathologique, Hôpital Armand Trousseau, Paris, 75012, France

    Liliane Boccon-Gibod

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  1. Dominique Baudry
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  2. Marine Faussillon
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Correspondence to Cécile Jeanpierre.

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Baudry, D., Faussillon, M., Cabanis, MO. et al. Changes in WT1 splicing are associated with a specific gene expression profile in Wilms' tumour. Oncogene 21, 5566–5573 (2002). https://doi.org/10.1038/sj.onc.1205752

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  • DOI: https://doi.org/10.1038/sj.onc.1205752

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