Project description:To investigate the heterogeneity of astrocyte progenitor subtypes present during human astrocyte differentiation that share molecular similarities with tumor initiating stem cells in GBM, we FACS isolated 4 populations of astrocytic progenitor subtypes as identified by the expression of cell surface markers CD51, CD63, and CD71 from three independent iPSC-derived neural progenitor cell lines.
Project description:To investigate the heterogeneity of astrocyte progenitor subtypes present during human astrocyte differentiation that share molecular similarities with tumor initiating stem cells in GBM.
Project description:Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma (WHO IV), its most malignant subtype, lower-grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notably variable clinical behavior. To examine the foundations of this heterogeneity, we performed multidimensional molecular profiling, including global transcriptional analysis, on 101 lower-grade diffuse astrocytic gliomas collected at our own institution, and validated our findings using publically available gene expression and copy number data from large independent patient cohorts. We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, PDGFRA overexpression, and prolonged survival, and IDH wild-type (IDH wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease outcome. Furthermore, global expression profiling revealed three robust molecular subclasses within lower-grade diffuse astrocytic gliomas, two of which were predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were distinguished from each other on the basis of TP53 mutations, DNA copy number abnormalities, and links to distinct stages of neurogenesis in the subventricular zone (SVZ). This latter finding implicates discrete pools of neuroglial progenitors as cells of origin for the different subclasses of IDH mt tumors. In summary, we have elucidated molecularly distinct subclasses of lower-grade diffuse astrocytic glioma that dictate clinical behavior and demonstrate fundamental associations with both IDH mutational status and neuroglial developmental stage. 80 tumor samples, one normal tissue sample (brain)
Project description:This study aims at investigating differential gene expression in human astrocytic tumours of grades I, II, III and IV. A total of 65 tumours were assessed using the Affymetrix U133A GeneChip. The study aims not only at discovering the main expression differences between astrocytic tumours of distinct histological grades but also wishes to correlate these findings with the known histopathological hallmarks of astrocytoma progression. Further, the study aims at correlating gene expression with previously obtained genomic information for several loci known to be involved in astrocytoma tumour progression.
Project description:This study aims at investigating differential gene expression in human astrocytic tumours of grades I, II, III and IV. A total of 65 tumours were assessed using the Affymetrix U133A GeneChip. The study aims not only at discovering the main expression differences between astrocytic tumours of distinct histological grades but also wishes to correlate these findings with the known histopathological hallmarks of astrocytoma progression. Further, the study aims at correlating gene expression with previously obtained genomic information for several loci known to be involved in astrocytoma tumour progression. Keywords: other
Project description:Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma (WHO IV), its most malignant subtype, lower-grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notably variable clinical behavior. To examine the foundations of this heterogeneity, we performed multidimensional molecular profiling, including global transcriptional analysis, on 101 lower-grade diffuse astrocytic gliomas collected at our own institution, and validated our findings using publically available gene expression and copy number data from large independent patient cohorts. We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, PDGFRA overexpression, and prolonged survival, and IDH wild-type (IDH wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease outcome. Furthermore, global expression profiling revealed three robust molecular subclasses within lower-grade diffuse astrocytic gliomas, two of which were predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were distinguished from each other on the basis of TP53 mutations, DNA copy number abnormalities, and links to distinct stages of neurogenesis in the subventricular zone (SVZ). This latter finding implicates discrete pools of neuroglial progenitors as cells of origin for the different subclasses of IDH mt tumors. In summary, we have elucidated molecularly distinct subclasses of lower-grade diffuse astrocytic glioma that dictate clinical behavior and demonstrate fundamental associations with both IDH mutational status and neuroglial developmental stage.
Project description:We identified three novel chromatin-driven subtypes of glioblastoma stem cells, regulated by specific essential transcription factors and with specific drug sensitivities.
Project description:This study aims at investigating differential gene expression in human diffusely infiltrating astrocytic tumours, grades II, III and IV. A total of 63 tumours were assessed using the Affymetrix U133A GeneChip. Samples comprised in this GEO submission are identical to those in submission GSE1993 with the exception of two pilocytic astrocytoma tumours (grade I) that have not been included. The study aims not only at discovering the main expression differences between astrocytic tumours of distinct histological grades but also wishes to correlate these findings with the known histopathological and biological hallmarks of astrocytoma progression. Further, the study aims at correlating gene expression with previously obtained genomic information for several loci known to be involved in astrocytoma tumour progression. Experiment Overall Design: A total of 63 tumours were assessed using the Affymetrix U133A GeneChip.