AN INTEGRATED VIEW OF THE TRANSCRIPTOME AND miRNOME OF GLIOBLASTOMA AND PERITUMOR TISSUES

Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumour. Despite multimodal aggressive treatment, the prognosis of GBM patients is poor and the median survival time after diagnosis is still in the range of just 12 months, with the interesting exception of a small fraction (less than 10%) of patients, referred to as long-term survivors (LTS), who survive longer than 36 months. In general, GBM recurrence occurs in peritumoral tissue in about 90% of patients, making this area a crucial one for studies about the molecular pathways perturbed early in GBM malignant evolution. By SAGE analysis, we have studied the transcriptome and miRNome of GBM tissues from 13 patients classified as either STS or LTS. For each patient, we have analysed one sample representing the center of the tumour (C) and another excised from the tumour-free peri-tumoral area (P). We describe a group of RNAs (coding and noncoding) found to be commonly modulated in P as well as in C samples compared to healthy white matter, that we think may represent early markers of GBM pathogenesis, and we also present RNAs that differentiate ST from LT tumors. Among upregulated RNAs in both comparisons, we have found a remarkable enrichment of mesenchymal-stem-like markers. For these comparisons, we will also show the relevant pathways affected by the modulated RNAs. Our data show that some genes and molecular pathways known to be perturbed in glioblastoma are already disrupted in the apparently tumor-free peri-tumor area, where it is conceivable that early tumor development occurs, predisposing cells to recurrence. Moreover, our results differentiating STS from LTS may help unravel the basis of this still elusive distinction.