Transcription profiling of human grade II astrocytic tumor (astrocytomas) vs grade IV tumors (glioblastoma)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Margareto Javier
PROVIDER: S-ECPF-MEXP-567 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Comparison of grade II astrocytic tumor (astrocytomas) with grade IV tumors (glioblastoma)
2007-03-01 | E-MEXP-567 | biostudies-arrayexpress
Project description:Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II-III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR-based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm-loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (-10q) were detected in IDH wild-type tumors. Kaplan-Meier estimates for progression-free survival showed that the tumors with mutant IDH, -1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild-type IDH, +7, or -10q. As tumors with +7 (IDH wild-type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management.
| S-EPMC4982592 | biostudies-literature
Project description:Diffuse astrocytoma of (WHO grade II) has a tendency to progress spontaneously to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). However, the molecular basis of astrocytoma progression is still poorly understood. In current study, an essential initial step toward this goal is the establishment of the taxonomy of tumors on the basis of their gene expression profiles. We have used gene expression profiling, unsupervised (hierarchal cluster (HCL) and principal component analysis (PCA)) and supervised (prediction analysis for microarrays (PAM)) learning methods, to demonstrate the presence of three distinct gene expression signatures of astrocytomas (ACMs), which correspond to diffuse or low-grade astrocytoma (WHO grade II), Anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV). We also demonstrate a 171 gene-based classifier that characterize the distinction between these pathologic/molecular subsets of astrocytomas. These results further define molecular subtypes of astrocytomas and may potentially be used to define potential targets and further refine stratification approaches for therapy. In addition, this study demonstrates that combining gene expression analysis with detailed annotated pathway and gene ontology (GO) category resources was applied to highly enriched normal and tumor population; it can yield an understanding of the critical biological mechanism of astrocytomas.
| S-EPMC3151497 | biostudies-literature
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.
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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.
| S-ECPF-GEOD-2727 | biostudies-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. 80 tumor samples, one normal tissue sample (brain)
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Project description:Comparison of the miRNAs profile of 8 WHO grade II gliomas and 24 higher grade tumors (2 WHO grade III and 22 glioblastomas) in order to identify the molecular determinants of progression.
| S-ECPF-MTAB-1840 | biostudies-other
Project description: Not available
| S-ECPF-GEOD-4271 | biostudies-other
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.
2008-06-12 | E-GEOD-1993 | biostudies-arrayexpress
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.
2008-06-12 | E-GEOD-2727 | biostudies-arrayexpress