Giambra Martina, Messuti Eleonora, Di Cristofori Andrea, Cavandoli Clarissa, Bruno Raffaele, Buonanno Raffaella, Marzorati Matilde, Zambuto Melissa, Rodriguez-Menendez Virginia, Redaelli Serena, Giussani Carlo, Bentivegna Angela
School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
Neurosurgery Unit, Department of Neuroscience, S. Gerardo Hospital, 20900 Monza, Italy.
Biology (Basel). 2021 Nov 9;10(11):1157. doi: 10.3390/biology10111157.
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.
胶质母细胞瘤是一种极其异质性的疾病。治疗失败和肿瘤复发主要反映了胶质瘤干细胞（GSCs）在肿瘤核心（TC）中的存在，其次是瘤周脑区（PBZ）的作用，其作用仍有待确定。利用阵列比较基因组杂交（array-CGH）平台，我们深化了关于胶质母细胞瘤不同成分的基因组知识，并鉴定出可用于新疗法的新的特异性生物标志物。我们首先研究了20个胶质母细胞瘤肿瘤核心的基因组图谱；然后，分别针对14例和7例病例，将这些基因组图谱与相关的胶质瘤干细胞培养物和瘤周脑区活检组织的图谱进行了比较。对20个肿瘤核心的分析证实了肿瘤间的异质性以及胶质母细胞瘤经典通路中高比例的拷贝数改变（CNAs）。比较14对肿瘤核心-胶质瘤干细胞的基因组图谱，我们发现每个患者的两个样本之间存在很强的相似性。如使用DAVID进行的生物信息学分析所示，共享的失衡基因与癌症的发生发展以及代谢途径有关。最后，7对肿瘤核心-瘤周脑区的比较导致鉴定出需要进一步研究的瘤周脑区独特改变。
