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Copy Number Defects of G1-Cell Cycle Genes in Neuroblastoma are Frequent and Correlate with High Expression of E2F Target Genes and a Poor Prognosis

Molenaar, Jan J.; Koster, Jan; Ebus, Marli E.; van Sluis, Peter; Westerhout, Ellen M.; de Preter, Katleen; Gisselsson Nord, David LU ; Øra, Ingrid LU ; Speleman, Frank and Caron, Huib N., et al. (2012) In Genes, Chromosomes and Cancer 51(1). p.10-19
Abstract
The tightly controlled network of cell cycle genes consists of a core of cyclin dependent kinases (CDKs) that are activated by periodically expressed cyclins. The activity of the cyclin-CDK complexes is regulated by cyclin dependent kinase inhibitors (CDKIs) and multiple signal transduction routes that converge on the cell cycle. Neuroblastoma are pediatric tumors that belong to the group of small round blue cell tumors, characterized by a fast proliferation. Here, we present high throughput analyses of cell cycle regulating genes in neuroblastoma. We analyzed a series of 82 neuroblastomas by comparative genomic hybridization arrays, single nucleotide polymorphism arrays, and Affymetrix expression arrays and analyzed the datasets in... (More)
The tightly controlled network of cell cycle genes consists of a core of cyclin dependent kinases (CDKs) that are activated by periodically expressed cyclins. The activity of the cyclin-CDK complexes is regulated by cyclin dependent kinase inhibitors (CDKIs) and multiple signal transduction routes that converge on the cell cycle. Neuroblastoma are pediatric tumors that belong to the group of small round blue cell tumors, characterized by a fast proliferation. Here, we present high throughput analyses of cell cycle regulating genes in neuroblastoma. We analyzed a series of 82 neuroblastomas by comparative genomic hybridization arrays, single nucleotide polymorphism arrays, and Affymetrix expression arrays and analyzed the datasets in parallel with the R2 bioinformatic tool (http://r2.amc.nl). About 30% of the tumors had genomic amplifications, gains, or losses with shortest regions of overlap that suggested implication of a series of G1 cell cycle regulating genes. CCND1 (cyclin D1) and CDK4 were amplified or gained and the chromosomal regions containing the CDKN2 (INK4) group of CDKIs were frequently deleted. Cluster analysis showed that tumors with genomic aberrations in G1 regulating genes over-expressed E2F target genes, which regulate S and G2/M phase progression. These tumors have a poor prognosis. Our findings suggest that pharmacological inhibition of cell cycle genes might bear therapeutic promises for patients with high risk neuroblastoma. (C) 2011 Wiley Periodicals, Inc. (Less)
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published
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Genes, Chromosomes and Cancer
volume
51
issue
1
pages
10 - 19
publisher
John Wiley & Sons
external identifiers
  • wos:000297545000002
  • scopus:80455150507
ISSN
1045-2257
DOI
10.1002/gcc.20926
language
English
LU publication?
yes
id
28183fe6-a550-4f8d-aa66-2b3d267fc60e (old id 2278933)
date added to LUP
2012-01-11 13:35:12
date last changed
2017-07-23 03:18:34
@article{28183fe6-a550-4f8d-aa66-2b3d267fc60e,
  abstract     = {The tightly controlled network of cell cycle genes consists of a core of cyclin dependent kinases (CDKs) that are activated by periodically expressed cyclins. The activity of the cyclin-CDK complexes is regulated by cyclin dependent kinase inhibitors (CDKIs) and multiple signal transduction routes that converge on the cell cycle. Neuroblastoma are pediatric tumors that belong to the group of small round blue cell tumors, characterized by a fast proliferation. Here, we present high throughput analyses of cell cycle regulating genes in neuroblastoma. We analyzed a series of 82 neuroblastomas by comparative genomic hybridization arrays, single nucleotide polymorphism arrays, and Affymetrix expression arrays and analyzed the datasets in parallel with the R2 bioinformatic tool (http://r2.amc.nl). About 30% of the tumors had genomic amplifications, gains, or losses with shortest regions of overlap that suggested implication of a series of G1 cell cycle regulating genes. CCND1 (cyclin D1) and CDK4 were amplified or gained and the chromosomal regions containing the CDKN2 (INK4) group of CDKIs were frequently deleted. Cluster analysis showed that tumors with genomic aberrations in G1 regulating genes over-expressed E2F target genes, which regulate S and G2/M phase progression. These tumors have a poor prognosis. Our findings suggest that pharmacological inhibition of cell cycle genes might bear therapeutic promises for patients with high risk neuroblastoma. (C) 2011 Wiley Periodicals, Inc.},
  author       = {Molenaar, Jan J. and Koster, Jan and Ebus, Marli E. and van Sluis, Peter and Westerhout, Ellen M. and de Preter, Katleen and Gisselsson Nord, David and Øra, Ingrid and Speleman, Frank and Caron, Huib N. and Versteeg, Rogier},
  issn         = {1045-2257},
  language     = {eng},
  number       = {1},
  pages        = {10--19},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Copy Number Defects of G1-Cell Cycle Genes in Neuroblastoma are Frequent and Correlate with High Expression of E2F Target Genes and a Poor Prognosis},
  url          = {http://dx.doi.org/10.1002/gcc.20926},
  volume       = {51},
  year         = {2012},
}