Pediatric rhabdoid tumors of kidney and brain show many differences in gene expression but share dysregulation of cell cycle and epigenetic effector genes
| Autor: | Purvi R. Patel, Bette K. Kleinschmidt-DeMasters, Andrew M. Donson, Michael H. Handler, Diane K. Birks, Elizabeth M. Algar, Alexandra Sufit, Nicholas K. Foreman, Rajeev Vibhakar, Christopher Dunham |
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| Rok vydání: | 2013 |
| Předmět: |
Genetics
Microarray Brain Neoplasms Microarray analysis techniques Cell Cycle Hematology Biology Article Kidney Neoplasms Chromatin remodeling Epigenesis Genetic Transcriptome Oncology Pediatrics Perinatology and Child Health Gene expression Cancer research Cluster Analysis Humans Epigenetics SMARCB1 Gene Rhabdoid Tumor Oligonucleotide Array Sequence Analysis |
| Zdroj: | Pediatric Blood & Cancer. 60:1095-1102 |
| ISSN: | 1545-5009 |
| DOI: | 10.1002/pbc.24481 |
| Popis: | 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. Pediatr Blood Cancer 2013; 60: 10951102. (c) 2013 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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