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Altered expression of cell cycle genes distinguishes aggressive neuroblastoma

Oncogene volume 24, pages 1533–1541 (2005)Cite this article

Abstract

In this study, gene expression profiling was performed on 103 neuroblastoma (NB) tumors, stages 1–4 with and without MYCN amplification, using cDNA microarrays containing 42 578 elements. Using principal component analysis (PCA) to analyse the relationships among these samples, we confirm that the global patterns of gene expression reflect the phenotype of the tumors. To explore the biological processes that may contribute to increasing aggressive phenotype of the tumors, we utilized a statistical approach based on PCA. We identified a specific subset of the cell cycle and/or chromosome segregation genes that distinguish stage 4 NB tumors from all lower stage tumors, including stage 3. Furthermore, the control of the kinetochore assembly emerges from the Gene Ontology analysis as one of the key biological processes associated with an aggressive NB phenotype. Finally, we establish that these genes are further upregulated in the most aggressive MYCN-amplified tumors.

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Abbreviations

NB:

neuroblastoma

ST1:

stage 1

ST2:

stage 2

ST3:

stage 3

NBMYCN-AMP:

MYCN amplified

NBMYCN-NA:

MYCN not amplified

PCA:

principal component analysis

GO:

gene ontology

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Acknowledgements

We thank Dr John Maris, and Children's Oncology Group (COG) and Dr Steven Qualman at the Cooperative Human Tissue Network for several of the tumors.

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Author notes

  1. Alexei L Krasnoselsky and Craig C Whiteford: These two authors contributed equally to this work

Authors and Affiliations

  1. Oncogenomics Section, Pediatric Oncology Branch, Advanced Technology Center, National Cancer Institute, 8717 Grovemont Circle, Gaithersburg, MD, 20877, USA

    Alexei L Krasnoselsky, Craig C Whiteford, Jun S Wei, Sven Bilke, Qing-Rong Chen & Javed Khan

  2. Department of Tumour Genetics – B030, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, D-69120, Germany

    Frank Westermann

Authors
  1. Alexei L Krasnoselsky
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  2. Craig C Whiteford
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  3. Jun S Wei
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  5. Frank Westermann
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  6. Qing-Rong Chen
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  7. Javed Khan
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Corresponding author

Correspondence to Javed Khan.

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Supplementary information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Krasnoselsky, A., Whiteford, C., Wei, J. et al. Altered expression of cell cycle genes distinguishes aggressive neuroblastoma. Oncogene 24, 1533–1541 (2005). https://doi.org/10.1038/sj.onc.1208341

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