Uncovering glioblastoma origin cells: Isolation and characterization from the subventricular zone

Glioblastoma (GBM), which has a poor prognosis despite aggressive treatments, likely originates from specific cells that acquire somatic mutations within the subventricular zone (SVZ), distant from the primary tumor site. However, the properties of GBM origin cells (OCs) residing in the SVZ remain largely unknown. In this study, we isolated and characterized GBM-OCs from the SVZ using a mouse model. Exome analyses of the mouse models revealed significant copy number alterations as GBM-OCs progressed to tumors in the model. RNA analysis of human SVZ samples from GBM patients identified chromosomal alterations (7 gain/10 loss), similar to those observed in early human GBM development. These alterations were predominantly found in neural stem cell-like (NSC-like), astrocyte-like (AC-like), and oligodendrocyte precursor cell-like (OPC-like) populations. This study identifies GBM-OCs in the SVZ of mice and humans, highlighting their distinct features, and suggests that these cells could serve as target cells for future GBM treatments. Overall design: A total of 211 samples were obtained from 103 patients were collected, including 140 GBM tissue samples, 42 SVZ and 21 brain cortex samples from GBM patients, and 8 SVZ tissue samples from non-GBM patients. The samples underwent RNA sequencing to evaluate gene expression profiles and possible gene copy alterations of each GBM tissue.