Pediatric rhabdoid tumors of kidney and brain show many differences in gene expression but share dysregulation of cell cycle and epigenetic effector genes

Diane K. Birks, Andrew M Donson, Purvi R. Patel, Alexandra Sufit, Elizabeth M. Algar, Christopher Dunham, B. K. Kleinschmidt-DeMasters, Michael H. Handler, Rajeev Vibhakar, Nicholas Olas K Foreman

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22 Citations (Scopus)

Abstract

Background: Rhabdoid tumors (RTs) are aggressive tumors of early childhood that occur most often in brain (AT/RTs) or kidney (KRTs). Regardless of location, they are characterized by loss of functional SMARCB1 protein, a component of the SWI/SNF chromatin remodeling complex. The aim of this study was to determine genes and biological process dysregulated in common to both AT/RTs and KRTs. Procedure: Gene expression for AT/RTs was compared to that of other brain tumors and normal brain using microarray data from our lab. Similar analysis was performed for KRTs and other kidney tumors and normal kidney using data from GEO. Dysregulated genes common to both analyses were analyzed for functional significance. Results: Unsupervised hierarchical clustering of RTs identified three major subsets: two comprised of AT/RTs, and one of KRTs. Compared to other tumors, 1,187, 663, and 539 genes were dysregulated in each subset, respectively. Only 14 dysregulated genes were common to all three subsets. Compared to normal tissue, 5,209, 4,275, and 2,841 genes were dysregulated in each subset, with an overlap of 610 dysregulated genes. Among these genes, processes associated with cell proliferation, MYC activation, and epigenetic dysregulation were common to all three RT subsets. Conclusions: The low overlap of dysregulated genes in AT/RTs and KRTs suggests that factors in addition to SMARCB1 loss play a role in determining subsequent gene expression. Drugs which target cell cycle or epigenetic genes may be useful in all RTs. Additionally, targeted therapies tailored to specific RT subset molecular profiles should be considered.

Original languageEnglish
Pages (from-to)1095-1102
Number of pages8
JournalPediatric Blood and Cancer
Volume60
Issue number7
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Keywords

  • Atypical teratoid/rhabdoid tumor
  • INI-1
  • Kidney rhabdoid tumor
  • Microarray
  • SMARCB1

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