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

Oncogene. 2002 Aug 15;21(36):5566-73. doi: 10.1038/sj.onc.1205752.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • DNA Primers / chemistry
  • Down-Regulation
  • Exons
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Kidney / metabolism
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • WT1 Proteins / genetics*
  • WT1 Proteins / metabolism
  • Wilms Tumor / genetics*
  • Wilms Tumor / metabolism
  • Wilms Tumor / pathology


  • DNA Primers
  • Neoplasm Proteins
  • Protein Isoforms
  • WT1 Proteins