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.
Highlights
Glioblastoma (GBM) is the most common malignant tumor of the brain
It has been shown that even in the absence of tumor cells, kinases involved in cell proliferation, migration and apoptosis are expressed in brain adjacent to-tumor (BAT) together with molecules linked to stemness, invasion and neo-angiogenesis, which might indicate that BAT is undergoing transformation [9,10,11]
By comparing the expression pattern of CTRL and BAT, we separated 57 genes which were differentially expressed in BAT against CTRL
Summary
Glioblastoma (GBM) is the most common malignant tumor of the brain. GBM rapidly proliferates and invades the central nervous system. It has been shown that even in the absence of tumor cells, kinases involved in cell proliferation, migration and apoptosis are expressed in BAT together with molecules linked to stemness, invasion and neo-angiogenesis, which might indicate that BAT is undergoing transformation [9,10,11]. To support this hypothesis, we carried out a gene expression profile and a genomic analysis of BAT to detect alterations that may indicate the appearance of neoplastic features. We have compared the gene expression profile of tissue samples from ET, BAT, and normal white matter (CTRL) and have analyzed the BAT with an Array-CGH to detect genomic alterations
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