Characterizing the Genomic Profile in High-Grade Gliomas: From Tumor Core to Peritumoral Brain Zone, Passing through Glioma-Derived Tumorspheres

SIMPLE SUMMARY: The genomic landscape of the stem cell compartment and peritumoral brain zone of glioblastoma is still incomplete. The key role of the stem component in tumor maintenance and progression, as well as in drug-resistance spreading, has already been demonstrated. In recent years, the importance of the marginal area of the neoplasm has been considered since this is where the tumor recurrences appear in up to 90% of cases. In this study, we carried out a 360° genomic profile analysis of the different glioblastoma components in order to understand how they are characterized and how they work. Studying their genomic constitution is the starting point necessary to finally develop target treatments associable with the standard ones, as a new hope for glioblastoma patients. ABSTRACT: Glioblastoma is an extremely heterogeneous disease. Treatment failure and tumor recurrence primarily reflect the presence in the tumor core (TC) of the glioma stem cells (GSCs), and secondly the contribution, still to be defined, of the peritumoral brain zone (PBZ). Using the array-CGH platform, we deepened the genomic knowledge about the different components of GBM and we identified new specific biomarkers useful for new therapies. We firstly investigated the genomic profile of 20 TCs of GBM; then, for 14 cases and 7 cases, respectively, we compared these genomic profiles with those of the related GSC cultures and PBZ biopsies. The analysis on 20 TCs confirmed the intertumoral heterogeneity and a high percentage of copy number alterations (CNAs) in GBM canonical pathways. Comparing the genomic profiles of 14 TC-GSC pairs, we evidenced a robust similarity among the two samples of each patient. The shared imbalanced genes are related to the development and progression of cancer and in metabolic pathways, as shown by bioinformatic analysis using DAVID. Finally, the comparison between 7 TC-PBZ pairs leads to the identification of PBZ-unique alterations that require further investigation.