Integrative genome-wide analysis reveals a robust genomic glioblastoma signature associated with copy number driving changes in gene expression.
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.
de Tayrac
Marie
M
Faculty of Medicine, CNRS-UMR 6061, Regulation of Transcription and Oncogenesis, IFR140 GFAS, Rennes, France.
Etcheverry
Amandine
A
Aubry
Marc
M
Saïkali
Stephan
S
Hamlat
Abderrahmane
A
Quillien
Veronique
V
Le Treut
André
A
Galibert
Marie-Dominique
MD
Mosser
Jean
J
D015820:Cadherins / Q000235:genetics; D002869:Chromosome Aberrations; D002874:Chromosome Mapping / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D020690:GTPase-Activating Proteins; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018773:Genes, erbB-1; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D053858:Metabolic Networks and Pathways; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000091363:Protocadherins; D025521:Tumor Suppressor Proteins / Q000235:genetics
D015820:Cadherins; D004273:DNA, Neoplasm; D020690:GTPase-Activating Proteins; C115817:PCDH9 protein, human; D000091363:Protocadherins; C473607:STARD13 protein, human; D025521:Tumor Suppressor Proteins