Human Gene Set: LI_WILMS_TUMOR


Standard name LI_WILMS_TUMOR
Systematic name M10773
Brief description 'Wilm's tumor signature': genes highly expressed in Wilm's tumor samples compared to normal fetal kidney and a heterologous tumor, Burkit lymphoma.
Full description or 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 E1AF.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12057921   Authors: Li CM,Guo M,Borczuk A,Powell CA,Wei M,Thaker HM,Friedman R,Klein U,Tycko B
Exact source Table 1: set C
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_HG_U95
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Version history 3.0: First introduced

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