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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 7/2012

01-07-2012 | Neuro-Oncology

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

Authors: Paola E. Leone, PhD, M. Belén González, PhD, Carolina Elosua, BS, Juan A. Gómez-Moreta, MD, Eva Lumbreras, BS, Cristina Robledo, PhD, Angel Santos-Briz, MD, José Maria Valero, MD, PhD, Rafael Díaz de la Guardia, PhD, Norma C. Gutiérrez, MD, PhD, Jesús M. Hernández, MD, PhD, Juan L. García, PhD

Published in: Annals of Surgical Oncology | Issue 7/2012

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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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Metadata
Title
Integration of Global Spectral Karyotyping, CGH Arrays, and Expression Arrays Reveals Important Genes in the Pathogenesis of Glioblastoma Multiforme
Authors
Paola E. Leone, PhD
M. Belén González, PhD
Carolina Elosua, BS
Juan A. Gómez-Moreta, MD
Eva Lumbreras, BS
Cristina Robledo, PhD
Angel Santos-Briz, MD
José Maria Valero, MD, PhD
Rafael Díaz de la Guardia, PhD
Norma C. Gutiérrez, MD, PhD
Jesús M. Hernández, MD, PhD
Juan L. García, PhD
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 7/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-2202-5

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