Clinically relevant subsets identified by gene expression patterns support a revised ontogenic model of Wilms tumor: A Children's Oncology Group study

Samantha L Gadd, Vicki Huff, Chiang Ching Huang, E. Cristy Ruteshouser, Jeffrey S. Dome, Paul E. Grundy, Norman Breslow, Lawrence J Jennings, Daniel M. Green, J. Bruce Beckwith, Elizabeth J Perlman

Research output: Contribution to journalArticle

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Abstract

Wilms tumors (WT) have provided broad insights into the interface between development and tumorigenesis. Further understanding is confounded by their genetic, histologic, and clinical heterogeneity, the basis of which remains largely unknown. We evaluated 224 WT for global gene expression patterns; WT1, CTNNB1, and WTX mutation; and 11p15 copy number and methylation patterns. Five subsets were identified showing distinct differences in their pathologic and clinical features: these findings were validated in 100 additional WT. The gene expression pattern of each subset was compared with published gene expression profiles during normal renal development. A novel subset of epithelial WT in infants lacked WT1, CTNNB1, and WTX mutations and nephrogenic rests and displayed a gene expression pattern of the postinduction nephron, and none recurred. Three subsets were characterized by a low expression of WT1 and intralobar nephrogenic rests. These differed in their frequency of WT1 and CTNNB1 mutations, in their age, in their relapse rate, and in their expression similarities with the intermediate mesoderm versus the metanephric mesenchyme. The largest subset was characterized by biallelic methylation of the imprint control region 1, a gene expression profile of the metanephric mesenchyme, and both interlunar and perilobar.

Original languageEnglish (US)
Pages (from-to)742-756
Number of pages15
JournalNeoplasia (United States)
Volume14
Issue number8
DOIs
StatePublished - Jan 1 2012

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Wilms Tumor
Mesoderm
Transcriptome
Gene Expression
Methylation
Mutation
Wilms' Tumor Genes
Nephrons
Carcinogenesis
Kidney
Recurrence

ASJC Scopus subject areas

  • Cancer Research

Cite this

Gadd, Samantha L ; Huff, Vicki ; Huang, Chiang Ching ; Cristy Ruteshouser, E. ; Dome, Jeffrey S. ; Grundy, Paul E. ; Breslow, Norman ; Jennings, Lawrence J ; Green, Daniel M. ; Bruce Beckwith, J. ; Perlman, Elizabeth J. / Clinically relevant subsets identified by gene expression patterns support a revised ontogenic model of Wilms tumor : A Children's Oncology Group study. In: Neoplasia (United States). 2012 ; Vol. 14, No. 8. pp. 742-756.
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Clinically relevant subsets identified by gene expression patterns support a revised ontogenic model of Wilms tumor : A Children's Oncology Group study. / Gadd, Samantha L; Huff, Vicki; Huang, Chiang Ching; Cristy Ruteshouser, E.; Dome, Jeffrey S.; Grundy, Paul E.; Breslow, Norman; Jennings, Lawrence J; Green, Daniel M.; Bruce Beckwith, J.; Perlman, Elizabeth J.

In: Neoplasia (United States), Vol. 14, No. 8, 01.01.2012, p. 742-756.

Research output: Contribution to journalArticle

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