title: Gene expression profile of glioblastoma peritumoral tissue: an ex vivo study.
abstract: The gene expression pattern of glioblastoma (GBM) is well documented but the expression profile of brain adjacent to tumor is not yet analysed. This may help to understand the oncogenic pathway of GBM development. We have established the genome-wide expression profiles of samples isolated from GBM tumor mass, white matter adjacent to tumor (apparently free of tumor cells), and white matter controls by using the Affymetrix HG-U133 arrays. Array-CGH (aCGH) was also performed to detect genomic alterations. Among genes dysregulated in peritumoral white matter, 15 were over-expressed, while 42 were down-regulated when compared to white matter controls. A similar expression profile was detected in GBM cells. Growth, proliferation and cell motility/adhesion-associated genes were up-regulated while genes involved in neurogenesis were down-regulated. Furthermore, several tumor suppressor genes along with the KLRC1 (a member of natural killer receptor) were also down-regulated in the peritumoral brain tissue. Several mosaic genomic lesions were detected by aCGH, mostly in tumor samples and several GBM-associated mosaic genomic lesions were also present in the peritumoral brain tissue, with a similar mosaicism pattern. Our data could be explained by a dilution of genes expressed from tumor cells infiltrating the peritumour tissue. Alternatively, these findings could be substained by a relevant amount of "apparently normal" cells presenting a gene profile compatible with a precancerous state or even "quiescent" cancer cells. Otherwise, the recurrent tumor may arise from both infiltrating tumor cells and from an interaction and recruitment of apparently normal cells in the peritumor tissue by infiltrating tumor cells.
authors.affiliation: Institute of Neurosurgery, Faculty of Medicine, Catholic University of Rome, Rome, Italy.
authors.forename: Annunziato
authors.initials: A
authors.lastname: Mangiola
authors.forename: Nathalie
authors.initials: N
authors.lastname: Saulnier
authors.forename: Pasquale
authors.initials: P
authors.lastname: De Bonis
authors.forename: Daniela
authors.initials: D
authors.lastname: Orteschi
authors.forename: Gigliola
authors.initials: G
authors.lastname: Sica
authors.forename: Gina
authors.initials: G
authors.lastname: Lama
authors.forename: Benedetta Ludovica
authors.initials: BL
authors.lastname: Pettorini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sabatino
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
authors.forename: Anna
authors.initials: A
authors.lastname: Colabianchi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Proietti
authors.forename: Gyula
authors.initials: G
authors.lastname: Kovacs
authors.forename: Giulio
authors.initials: G
authors.lastname: Maira
authors.forename: Carmelo
authors.initials: C
authors.lastname: Anile
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome