Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition

Chi Ming Li, Meirong Guo, Alain Borczuk, Charles A. Powell, Michelle Wei, Harshwardhan Thaker, Richard Friedman, Ulf Klein, Benjamin Tycko

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

Wilms' tumor (WT) has been considered a prototype for arrested cellular differentiation in cancer, but previous studies have relied on selected markers. We have now performed an unbiased survey of gene expression in WTs using oligonucleotide microarrays. Statistical criteria identified 357 genes as differentially expressed between WTs and fetal kidneys. This set contained 124 matches to genes on a microarray used by Stuart and colleagues (Stuart RO, Bush KT, Nigam SK: Changes in global gene expression patterns during development and maturation of the rat kidney. Proc Natl Acad Sci USA 2001, 98:5649-5654) to establish genes with stage-specific expression in the developing rat kidney. Mapping between the two data sets showed that WTs systematically overexpressed genes corresponding to the earliest stage of metanephric development, and underexpressed genes corresponding to later stages. Automated clustering identified a smaller group of 27 genes that were highly expressed in WTs compared to fetal kidney and heterologous tumor and normal tissues. This signature set was enriched in genes encoding transcription factors. Four of these, PAX2, EYA1, HBF2, and HOXA11, are essential for cell survival and proliferation in early metanephric development, whereas others, including SIX1, MOX1, and SALL2, are predicted to act at this stage. SIX1 and SALL2 proteins were expressed in the condensing mesenchyme in normal human fetal kidneys, but were absent (SIX1) or reduced (SALL2) in cells at other developmental stages. These data imply that the blastema in WTs has progressed to the committed stage in the mesenchymal-epithelial transition, where it is partially arrested in differentiation. The WT-signature set also contained the Wnt receptor FZD7, the tumor antigen PRAME, the imprinted gene NNAT and the metastasis-associated transcription factor EIAF.

Original languageEnglish (US)
Pages (from-to)2181-2190
Number of pages10
JournalAmerican Journal of Pathology
Volume160
Issue number6
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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Epithelial-Mesenchymal Transition
Wilms Tumor
Gene Expression
Genes
Kidney
Transcription Factors
Wnt Receptors
Neoplasm Antigens
Mesoderm
Oligonucleotide Array Sequence Analysis
Cluster Analysis
Neoplasms
Cell Survival
Cell Proliferation
Neoplasm Metastasis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. / Li, Chi Ming; Guo, Meirong; Borczuk, Alain; Powell, Charles A.; Wei, Michelle; Thaker, Harshwardhan; Friedman, Richard; Klein, Ulf; Tycko, Benjamin.

In: American Journal of Pathology, Vol. 160, No. 6, 01.01.2002, p. 2181-2190.

Research output: Contribution to journalArticle

Li, Chi Ming ; Guo, Meirong ; Borczuk, Alain ; Powell, Charles A. ; Wei, Michelle ; Thaker, Harshwardhan ; Friedman, Richard ; Klein, Ulf ; Tycko, Benjamin. / Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. In: American Journal of Pathology. 2002 ; Vol. 160, No. 6. pp. 2181-2190.
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