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Integration of Global Spectral Karyotyping, CGH Arrays, and Expression Arrays Reveals Important Genes in the Pathogenesis of Glioblastoma Multiforme

  • Neuro-Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Glioblastoma multiforme (GBM) is the most common primary tumor of the central nervous system in adults. Patients with GBM have few treatment options, and their disease is invariably fatal. Molecularly targeted agents offer the potential to improve patient treatment; however, the use of these will require a fuller understanding of the genetic changes in this complex tumor.

Methods

We analyzed a series of 32 patients with GBM with array comparative genomic hybridization in combination with gene expression analysis. We focused on the recurrent breakpoints found by spectral karyotyping (SKY).

Results

By SKY we identified 23 recurrent breakpoints of the 202 translocations found in GBM cases. Gains and losses were identified in chromosomal regions close to the breakpoints by array comparative genomic hybridization. We evaluated the genes located in the regions involved in the breakpoints in depth. A list of 406 genes that showed a level of expression significantly different between patients and control subjects was selected to determine their effect on survival. Genes CACNA2D3, PPP2R2B, SIK, MAST3, PROM1, and PPP6C were significantly associated with shorter survival (median 200 days vs. 450 days, P ≤ 0.03).

Conclusions

We present a list of genes located in regions of breakpoints that could be grounds for future studies to determine whether they are crucial in the pathogenesis of this type of tumor, and we provide a list of six genes associated with the clinical outcome of patients with GBM.

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Acknowledgment

We thank Maria Angeles Hernandez for technical assistance. Research grants and financial support included the following: research in P.E.L.’s laboratory is supported by the ISCIII-CSJA (EMER07/054); and research in J.L.G.’s laboratory is supported by the ISCIII-CSJCyL (EMER07/038).

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Authors and Affiliations

  1. Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC, Salamanca, Spain

    Paola E. Leone PhD, M. Belén González PhD, Eva Lumbreras BS, Cristina Robledo PhD, Norma C. Gutiérrez MD, PhD, Jesús M. Hernández MD, PhD & Juan L. García PhD

  2. Andalusian Stem Cell Bank, Cytogenetic and Molecular Biology Group, Centre for Biomedical Research, Granada, Spain

    Paola E. Leone PhD, Carolina Elosua BS & Rafael Díaz de la Guardia PhD

  3. Servicio de Neurocirugía, Hospital Universitario de Salamanca, Salamanca, Spain

    Juan A. Gómez-Moreta MD

  4. Servicio de Anatomía Patológica, Hospital Universitario de Salamanca, Salamanca, Spain

    Angel Santos-Briz MD

  5. Instituto de Estudio de Ciencias de la Salud de Castilla y León (IECSCYL), Hospital Universitario de Salamanca, Salamanca, Spain

    José Maria Valero MD, PhD & Juan L. García PhD

  6. Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain

    Norma C. Gutiérrez MD, PhD & Jesús M. Hernández MD, PhD

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  1. Paola E. Leone PhD
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  2. M. Belén González PhD
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  3. Carolina Elosua BS
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  4. Juan A. Gómez-Moreta MD
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  6. Cristina Robledo PhD
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  7. Angel Santos-Briz MD
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  8. José Maria Valero MD, PhD
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  9. Rafael Díaz de la Guardia PhD
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  10. Norma C. Gutiérrez MD, PhD
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  12. Juan L. García PhD
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Correspondence to Paola E. Leone PhD or Juan L. García PhD.

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Leone, P.E., González, M.B., Elosua, C. et al. Integration of Global Spectral Karyotyping, CGH Arrays, and Expression Arrays Reveals Important Genes in the Pathogenesis of Glioblastoma Multiforme. Ann Surg Oncol 19, 2367–2379 (2012). https://doi.org/10.1245/s10434-011-2202-5

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  • DOI: https://doi.org/10.1245/s10434-011-2202-5

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