Characterization of the mutational landscape of high-grade gliomas in a Latin American cohort
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE252870 | GEO | 2024/06/30
REPOSITORIES: GEO
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Project description:Migrated from 1.6 id: 1015897590491013 GEDP id: 760 In current clinical practice, histology-based grading of diffuse infiltrative gliomas is the best predictor of patient survival time. Yet histology provides little insight into the underlying biology of gliomas and is limited in its ability to identify and guide new molecularly targeted therapies. We have performed large-scale gene expression analysis using the Affymetrix HG U133 oligonucleotide arrays on 85 diffuse infiltrating gliomas of all histologic types to assess whether a gene expression-based, histology-independent classifier is predictive of survival and to determine whether gene expression signatures provide insight into the biology of gliomas. We found that gene expression-based grouping of tumors is a more powerful survival predictor than histologic grade or age. The poor prognosis samples could be grouped into three different poor prognosis groups, each with distinct molecular signatures. We further describe a list of 44 genes whose expression patterns reliably classify gliomas into previously unrecognized biological and prognostic groups: these genes are outstanding candidates for use in histology-independent classification of high-grade gliomas. The ability of the large scale and 44 gene set expression signatures to group tumors into strong survival groups was validated with an additional external and independent data set from another institution composed of 50 additional gliomas. This demonstrates that large-scale gene expression analysis and subset analysis of gliomas reveals unrecognized heterogeneity of tumors and is efficient at selecting prognosis-related gene expression differences which are able to be applied across institutions. nelso-00262 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG-U133A, HG-U133B Organism: Homo sapiens (ncbitax) Material Types: total RNA, synthetic_RNA, organism_part, whole_organism Disease States: Glioma, Glioblastoma, Oligodendroglial Tumor, astrocytomas
2016-06-14 | E-GEOD-83294 | biostudies-arrayexpress
Project description:Congenital glioblastoma multiforme (cGBM) historically has been considered an aggressive tumor of infancy requiring extensive chemotherapy to achieve cure. We report on 4 patients at our institution with cGBMs who were treated with surgery and chemotherapy (carboplatin and etoposide every 21 days for 2-6 cycles). Four of four patients are progression free at a median time of 27.5 months (22-103 months). To characterize the molecular biology of cGBM, we compared the gene expression profiles of 3 cGBMs to 12 pediatric and 6 primary adult glioblastomas collected at our institution. Unsupervised hierarchical clustering showed cGBMs grouped together with other high-grade gliomas. cGBMs demonstrated marked similarity to both pediatric and adult GBMs, with only a total of 31 differentially expressed genes identified (FDR < 0.05). Unique molecular features of congenital GBMs identified included over-expression of multiple genes involved in glucose metabolism and tissue hypoxia pathways. Four tyrosine kinases were also mong the up-regulated genes (RET, RASGRF2, EFNA5, ALK). Thus, at our institution congenital GBMs, while similar both histologically and molecularly to other GBMs, appear to have a good prognosis with surgery in combination with relatively moderate chemotherapy. Further study is needed to determine if the few gene expression differences that were identified may contribute to the better survival seen in these tumors compared to pediatric or adult GBMs. Key Words: glioblastoma; congenital; pediatric; gene expression; microarray
2012-05-21 | GSE32374 | GEO
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)
2012-02-24 | E-GEOD-35158 | biostudies-arrayexpress
Project description:Congenital glioblastoma multiforme (cGBM) historically has been considered an aggressive tumor of infancy requiring extensive chemotherapy to achieve cure. We report on 4 patients at our institution with cGBMs who were treated with surgery and chemotherapy (carboplatin and etoposide every 21 days for 2-6 cycles). Four of four patients are progression free at a median time of 27.5 months (22-103 months). To characterize the molecular biology of cGBM, we compared the gene expression profiles of 3 cGBMs to 12 pediatric and 6 primary adult glioblastomas collected at our institution. Unsupervised hierarchical clustering showed cGBMs grouped together with other high-grade gliomas. cGBMs demonstrated marked similarity to both pediatric and adult GBMs, with only a total of 31 differentially expressed genes identified (FDR < 0.05). Unique molecular features of congenital GBMs identified included over-expression of multiple genes involved in glucose metabolism and tissue hypoxia pathways. Four tyrosine kinases were also mong the up-regulated genes (RET, RASGRF2, EFNA5, ALK). Thus, at our institution congenital GBMs, while similar both histologically and molecularly to other GBMs, appear to have a good prognosis with surgery in combination with relatively moderate chemotherapy. Further study is needed to determine if the few gene expression differences that were identified may contribute to the better survival seen in these tumors compared to pediatric or adult GBMs. Key Words: glioblastoma; congenital; pediatric; gene expression; microarray Molecular profiling of 18 AT/RT patient tumor samples was performed using Affymetrix U133 Plus2 GeneChips. Data were background corrected and normalized using gcRMA (as implemented in Bioconductor). Unsupervised agglomerative hierarchical clustering was performed to identify subsets of AT/RTs with similar gene expression. Limma (moderated t-tests; Bioconductor) was used to identify signature genes for each cluster. Bioinformatics web tool DAVID was used to identify enriched biological processes for each cluster. Survival was analyzed using Kaplan-Meier curves and Cox Hazard Ratio. Bioinformatics tools Gene Set Enrichment (GSEA) and Ingenuity Pathways Analysis were also used to gain further insight into cluster differences.
2012-05-20 | E-GEOD-32374 | biostudies-arrayexpress
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.
2012-02-24 | GSE35158 | GEO
Project description:We have used Illumina Infinium HumanMethylation450 BeadChip array profiling to profile paediatric high grade gliomas and diffuse intrinsic pontine gliomas. The 450K methylation array is being used to separate brain tumour samples on the basis of their methylation profiles which represent the cell of origin the time and place in which tumours arise. Methylation arrays provide data for an integrated molecular diagnosis of brain tumours and define specific molecular subgroups and subtypes of high grade gliomas carrying distinct driver mutations and patterns of somatic alterations. These data form part of an integrated meta-analysis of high grade gliomas in children combining DNA copy number, methylation and high throughput sequencing datasets.
2017-09-28 | E-MTAB-5528 | biostudies-arrayexpress
Project description:Astrocytomas are heterogeneous intracranial glial neoplasms ranging from the highly aggressive malignant glioblastoma multiforme (GBM) to the indolent, low-grade pilocytic astrocytoma. We have investigated whether DNA microarrays can identify gene expression differences between high-grade and low-grade glial tumors. We compared the transcriptional profile of 45 astrocytic tumors including 21 GBMs and 19 pilocytic astrocytomas using oligonucleotide-based microarrays. Of the approximately 6800 genes that were analyzed, a set of 360 genes provided a molecular signature that distinguished between GBMs and pilocytic astrocytomas. Many transcripts that were increased in GBM were not previously associated with gliomas and were found to encode proteins with properties that suggest their involvement in cell proliferation or cell migration. Microarray-based data for a subset of genes was validated using real-time quantitative reverse transcription-PCR. Immunohistochemical analysis also localized the protein products of specific genes of interest to the neoplastic cells of high-grade astrocytomas. Our study has identified a large number of novel genes with distinct expression patterns in high-grade and low-grade gliomas. hanas-00078 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Tissue Sites: Brain Material Types: synthetic_DNA, synthetic_RNA, organism_part Disease States: Primary Glioma, Normal
2015-06-25 | E-GEOD-70231 | biostudies-arrayexpress
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2023-12-13 | GSE232469 | GEO
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2014-09-26 | E-GEOD-61710 | biostudies-arrayexpress
Project description:Glioma, a prevalent and deadly brain tumor, is marked by significant cellular heterogeneity and metabolic alterations, yet the comprehensive cell-of-origin and metabolic landscape in high-grade (Glioblastoma Multiforme, WHO grade IV) and low-grade (Oligoastrocytoma, WHO grade II) gliomas remains elusive. In this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for their clinical significance.
2024-06-21 | GSE270109 | GEO