Molecular analyses of glioblastoma stem-like cells and glioblastoma tissue

Abstract

Glioblastoma is a common, malignant brain tumor whose disease incidence increases with age. Glioblastoma stem-like cells (GSCs) are thought to contribute to cancer therapy resistance and to be responsible for tumor initiation, maintenance, and recurrence. This study utilizes both SNP array and gene expression profiling to better understand GSCs and their relation to malignant disease. Peripheral blood and primary glioblastoma tumor tissue were obtained from patients, the latter of which was used to generate GSCs as well as a CD133 pos. /CD15 pos. subpopulation. The stem cell features of GSCs were confirmed via the immunofluorescent expression of Nestin, SOX2, and CD133. Both tumor tissue and the isolated primary cells shared unique abnormal genomic characteristics, including a gain of chromosome 7 as well as either a partial or complete loss of chromosome 10. Individual genomic differences were also observed, including the loss of chromosome 4 and segmental uniparental disomy of 9p24.3→p21.3 in GSCs. Gene expression profiling revealed 418 genes upregulated in tumor tissue vs. CD133 pos. /CD15 pos. cells and 44 genes upregulated in CD133 pos. /CD15 pos. cells vs. tumor tissue. Pathway analyses demonstrated that upregulated genes in CD133 pos. /CD15 pos. cells are relevant to cell cycle processes and cancerogenesis. In summary, we detected previously undescribed genomic and gene expression differences when comparing tumor tissue and isolated stem-like subpopulations.

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

“…They also share many of the molecular markers commonly used to isolate and identify NSCs [ 15 ]. However, GSCs differ from NSCs in their genetic mutational profiles, chromosomal abnormalities, and tumorigenicity [ 15 , 17 ]. They are also characterized by their low abundance within the tumor and low proliferative activity, which protects them from therapies targeting dividing cells [ 18 ].…”

Molecular Mechanisms of Drug Resistance in Glioblastoma

“…A comparison of tumor tissue and isolated stem-like subpopulations revealed 418 genes upregulated in tumor tissue with respect to CD133-positive/CD15-positive cells and 44 genes upregulated in CD133-positive/CD15-positve cells with respect to tumor tissue. These upregulated genes are relevant to the cell division cycle and oncogenesis [51]. In general, receptor tyrosine kinases (RTKs) are dysregulated in approximately 90% of GBM, and often plateletderived growth factor receptor (PDGFR) and epidermal growth factor receptor (EGFR) are amplified or mutated in GBM [52,53].…”

Development of a nomogram based on radiomics and semantic features for predicting chromosome 7 gain/chromosome 10 loss in IDH wild-type histologically low-grade gliomas

“…The LGG is characterized by a widespread malignant potential and primarily affects young people, with a median overall survival of approximately 7 years ( 1 ). GBM is extremely malignant and mainly affects the elderly, with a median survival of only 8 months after diagnosis ( 2 , 3 ). Gliomas have a unique genomic profile, and molecular markers have been identified as an essential basis for glioma classification in the 2021 WHO Classification of Central Nervous System Tumors.…”