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Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia

Oncogene volume 24, pages 457–468 (2005)Cite this article

Abstract

Anaplasia (unfavorable histology) is associated with therapy resistance and poor prognosis of Wilms tumor, but the molecular basis for this phenotype is unclear. Here, we used a cDNA array with 9240 clones relevant to cancer biology and/or kidney development to examine the expression profiles of 54 Wilms tumors, five normal kidneys and fetal kidney. By linking genes differentially expressed between fetal kidney and Wilms tumors to kidney morphogenesis, we found that genes expressed at a higher level in Wilms tumors tend to be expressed more in uninduced metanephrogenic mesenchyme or blastema than in their differentiated structures. Conversely, genes expressed at a lower level in Wilms tumors tend to be expressed less in uninduced metanephrogenic mesenchyme or blastema. We also identified 97 clones representing 76 Unigenes or unclustered ESTs that clearly separate anaplastic Wilms tumors from tumors with favorable histology. Genes in this set provide insight into the nature of the abnormal nuclear morphology of anaplastic tumors and may facilitate identification of molecular targets to improve their responsiveness to treatment.

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Abbreviations

FH:

favorable histology

UTR:

untranslated region

CT:

cycle of threshold

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Acknowledgements

We thank Dr Patricia Stanhope-Baker for critical comments on the manuscript, Dr Marek Skacel for the construction of the Wilms tumor tissue microarray, and Drs Herman Yeger and Jennifer Alami from the Hospital for Sick Children (Toronto, Canada) and the National Wilms Tumor Study Group for providing Wilms tumor specimens. The work was supported by National Institutes of Health Grant R01-CA89279 to BRGW.

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Authors and Affiliations

  1. Department of Genetics, Case Western Reserve University, Cleveland, OH, USA

    Wenliang Li & Bryan R G Williams

  2. Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Wenliang Li, Patricia Kessler & Bryan R G Williams

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  1. Wenliang Li
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Correspondence to Bryan R G Williams.

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Li, W., Kessler, P. & Williams, B. Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia. Oncogene 24, 457–468 (2005). https://doi.org/10.1038/sj.onc.1208228

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