Research Article

Segmental chromosome aberrations converge on overexpression of mitotic spindle regulatory genes in high-risk neuroblastoma

  1. Wen Fong Ooi1,†,
  2. Angela Re1,†,
  3. Viktoryia Sidarovich1,
  4. Valentina Canella1,
  5. Natalia Arseni1,
  6. Valentina Adami2,
  7. Giulia Guarguaglini3,
  8. Maria Giubettini3,
  9. Paola Scaruffi4,5,
  10. Sara Stigliani4,
  11. Patrizia Lavia3,
  12. Gian Paolo Tonini4,
  13. Alessandro Quattrone1,*

Article first published online: 15 FEB 2012

DOI: 10.1002/gcc.21940

Issue

Genes, Chromosomes and Cancer

Genes, Chromosomes and Cancer

Volume 51, Issue 6, pages 545–556, June 2012

Additional Information

How to Cite

Ooi, W. F., Re, A., Sidarovich, V., Canella, V., Arseni, N., Adami, V., Guarguaglini, G., Giubettini, M., Scaruffi, P., Stigliani, S., Lavia, P., Tonini, G. P. and Quattrone, A. (2012), Segmental chromosome aberrations converge on overexpression of mitotic spindle regulatory genes in high-risk neuroblastoma. Genes Chromosom. Cancer, 51: 545–556. doi: 10.1002/gcc.21940

Author Information

  1. 1

    Laboratory of Translational Genomics, Centre for Integrative Biology and Department of Information Engineering and Computer Science, University of Trento, 38122 Trento, Italy

  2. 2

    High Throughput Screening Facility, Centre for Integrative Biology, University of Trento, 38122 Trento, Italy

  3. 3

    Institute of Molecular Biology and Pathology, CNR, c/o Sapienza University of Rome, 00185 Rome, Italy

  4. 4

    Translational Oncopathology, National Cancer Research Institute (IST), 16132 Genoa, Italy

  5. 5

    Center of Physiopathology of Human Reproduction, Department of Obstetrics and Gynecology, “San Martino” Hospital, 16132 Genoa, Italy

  1. †

    These authors contributed equally to this work.

*Laboratory of Translational Genomics, for Integrative Biology, University of Trento, 38122 Trento, Italy

  1. †

    These authors contributed equally to this work.

Publication History

  1. Issue published online: 6 APR 2012
  2. Article first published online: 15 FEB 2012
  3. Manuscript Accepted: 7 JAN 2012
  4. Manuscript Revised: 6 JAN 2012
  5. Manuscript Received: 28 AUG 2011

Funded by

  • The Autonomous Province of Trento () [http://www.provincia.tn.it]
  • The Associazione Italiana per la Lotta al Neuroblastoma () [http://www.neuroblastoma.org]

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (1764K)

Abstract

Integration of genome-wide profiles of DNA copy number alterations (CNAs) and gene expression variations (GEVs) could provide combined power to the identification of driver genes and gene networks in tumors. Here we merge matched genome and transcriptome microarray analyses from neuroblastoma samples to derive correlation patterns of CNAs and GEVs, irrespective of their genomic location. Neuroblastoma correlation patterns are strongly asymmetrical, being on average 10 CNAs linked to 1 GEV, and show the widespread prevalence of long range covariance. Functional enrichment and network analysis of the genes covarying with CNAs consistently point to a major cell function, the regulation of mitotic spindle assembly. Moreover, elevated expression of 14 key genes promoting this function is strongly associated to high-risk neuroblastomas with 1p loss and MYCN amplification in a set of 410 tumor samples (P < 0.00001). Independent CNA/GEV profiling on neuroblastoma cell lines shows that increased levels of expression of these genes are linked to 1p loss. By this approach, we reveal a convergence of clustered neuroblastoma CNAs toward increased expression of a group of prognostic and functionally cooperating genes. We therefore propose gain of function of the spindle assembly machinery as a lesion potentially offering new targets for therapy of high-risk neuroblastoma. © 2012 Wiley Periodicals, Inc.

View Full Article with Supporting Information (HTML) Get PDF (1764K)