Integrative genome-wide analysis reveals a robust genomic glioblastoma signature associated with copy number driving changes in gene expression

Authors

  • Marie de Tayrac,

    1. CNRS-UMR 6061, Regulation of Transcription and Oncogenesis, IFR140 GFAS, Faculty of Medicine, Rennes, France
    2. Department of Biochemistry and Molecular Genetics, Medical Genomic Unit, CHU Rennes, France
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  • Amandine Etcheverry,

    1. Transcriptomic Platform, OUEST-Genopole®, Rennes, France
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  • Marc Aubry,

    1. Transcriptomic Platform, OUEST-Genopole®, Rennes, France
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  • Stephan Saïkali,

    1. Department of Pathology, CHRU Pontchaillou, Rennes, France
    2. Biological Ressource Center, CHRU Pontchaillou, Rennes, France
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  • Abderrahmane Hamlat,

    1. Department of Neurosurgery, CHRU Pontchaillou, Rennes, France
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  • Veronique Quillien,

    1. CNRS-UMR 6061, Regulation of Transcription and Oncogenesis, IFR140 GFAS, Faculty of Medicine, Rennes, France
    2. CRLCC, Centre Eugene Marquis, Rennes, France
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  • André Le Treut,

    1. CNRS-UMR 6061, Regulation of Transcription and Oncogenesis, IFR140 GFAS, Faculty of Medicine, Rennes, France
    2. Department of Biochemistry and Molecular Genetics, Medical Genomic Unit, CHU Rennes, France
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  • Marie-Dominique Galibert,

    1. CNRS-UMR 6061, Regulation of Transcription and Oncogenesis, IFR140 GFAS, Faculty of Medicine, Rennes, France
    2. Department of Biochemistry and Molecular Genetics, Medical Genomic Unit, CHU Rennes, France
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  • Jean Mosser

    Corresponding author
    1. CNRS-UMR 6061, Regulation of Transcription and Oncogenesis, IFR140 GFAS, Faculty of Medicine, Rennes, France
    2. Department of Biochemistry and Molecular Genetics, Medical Genomic Unit, CHU Rennes, France
    3. Transcriptomic Platform, OUEST-Genopole®, Rennes, France
    • Faculté de Médecine, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France
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Abstract

Glioblastoma multiforme shows multiple chromosomal aberrations, the impact of which on gene expression remains unclear. To investigate this relationship and to identify putative initiating genomic events, we integrated a paired copy number and gene expression survey in glioblastoma using whole human genome arrays. Loci of recurrent copy number alterations were combined with gene expression profiles obtained on the same tumor samples. We identified a set of 406 “cis-acting DNA targeted genes” corresponding to genomic aberrations with direct copy-number-driving changes in gene expression, defined as genes with either significantly concordant or correlated changes in DNA copy number and expression. Functional annotation revealed that these genes participate in key processes of cancer cell biology, providing insights into the genetic mechanisms driving glioblastoma. The robustness of the gene selection was validated on an external microarray data set including 81 glioblastomas and 23 non-neoplastic brain samples. The integration of array CGH and gene expression data highlights a robust cis-acting DNA targeted genes signature that may be critical for glioblastoma progression, with two tumor suppressor genes PCDH9 and STARD13 that could be involved in tumor invasiveness and resistance to etoposide. © 2008 Wiley-Liss, Inc.

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