Whole-genome bisulfite sequencing analysis of low-grade astrocytomas in the ICGC PedBrain Tumor Project
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PROVIDER: EGAS00001004019 | EGA |
REPOSITORIES: EGA
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Project description:Pilocytic astrocytomas (PAs) are the most common glioma in children. While many PAs; are slow growing or clinically indolent, others exhibit more aggressive features with tumor; recurrence and death. In order to identify genetic signatures that might predict PA clinical; behavior, we performed gene expression profiling on 41 primary PAs arising sporadically and in; patients with neurofibromatosis type 1 (NF1). While no expression signature was found that; could discriminate clinically-aggressive or recurrent tumors from more indolent cases, PAs; arising in patients with NF1 did exhibit a unique gene expression pattern. In addition, we; identified a gene expression signature that stratified PAs by location (supratentorial versus; infratentorial). Experiment Overall Design: 41 pilocytic astrocytoma samples were analyzed.
2008-06-14 | E-GEOD-5675 | biostudies-arrayexpress
Project description:<p>Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) program that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.</p> <p>Note that 931 out of 1234 samples in the Sequence Read Archive (SRA) passed QC and have transcript count data available from the Broad Institute Single Cell Portal. The transcript count data can be found at <a href="https://singlecell.broadinstitute.org/single_cell/study/SCP271/pilocytic-astrocytoma-single-cell-rna-seq#study-download" target="_blank">https://singlecell.broadinstitute.org/single_cell/study/SCP271/pilocytic-astrocytoma-single-cell-rna-seq#study-download</a></p>
| phs001854 | dbGaP
Project description:Pilocytic astrocytomas (PAs) are the most common glioma in children. While many PAs are slow growing or clinically indolent, others exhibit more aggressive features with tumor recurrence and death. In order to identify genetic signatures that might predict PA clinical behavior, we performed gene expression profiling on 41 primary PAs arising sporadically and in patients with neurofibromatosis type 1 (NF1). While no expression signature was found that could discriminate clinically-aggressive or recurrent tumors from more indolent cases, PAs arising in patients with NF1 did exhibit a unique gene expression pattern. In addition, we identified a gene expression signature that stratified PAs by location (supratentorial versus infratentorial). Keywords: Human, WHO grade I, Brain tumor, Pilocytic astrocytoma, NF1
2007-03-14 | GSE5675 | GEO
Project description:Pilocytic astrocytoma (PA) is a low-grade neoplasm frequently found in childhood. PA is characterized by slow growth and a relatively good prognosis. Genetic mechanisms such as activation of MAPK, BRAF gene deregulation and neurofibromatosis type 1 (NF1) syndrome have been associated with PA development. Epigenetic signature and miRNA expression profile are providing new insights about different types of tumor, including PAs. In the present study we evaluated global miRNA expression in 16 microdissected pediatric PA specimens, three NF1-associated PAs and 11 cerebral white matter (WM) samples by the microarray method. An additional cohort of 20 PAs was used to validate by qRT-PCR the expression of six miRNAs differentially expressed in the microarray data. Unsupervised hierarchical clustering analysis distinguished one cluster with nine PAs, including all NF1 cases and a second group consisting of the WM samples and seven PAs. Among 88 differentially expressed miRNAs between PAs and WM samples, the most underexpressed ones regulate classical pathways of tumorigenesis, while the most overexpressed miRNAs are related to pathways such as focal adhesion, P53 signaling pathway and gliomagenesis. The PAs/NF1 presented a subset of underexpressed miRNAs, which was also associated with known deregulated pathways in cancer such as cell cycle and hippo pathway. In summary, our data demonstrate that PA harbors at least two distinct miRNA signatures, including a subgroup of patients with NF1/PA lesions.
2019-08-01 | GSE135189 | GEO
Project description:Genome wide DNA methylation profiling of 79 histologically diagnosed pilocytic astrocytoma (PA) in adults, of which we were able to upload 71 samples. The methylation profiling indicates that many of the histologically diagnosed PA do not show a concordant methylation classification.
2024-01-01 | GSE244566 | GEO
Project description:Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a good prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. Potential biomarkers for PA patients, especially the non-BRAF-mutated ones are needed. Cerebrospinal fluid (CSF) is a valuable source of brain tumor biomarkers. Extracellular vesicles express valuable disease targets. These can be isolated from CSF from waste extraventricular drainage (EVD). We analyzed the proteome of EVD CSF from 24 PA, cerebral hemorrhage (CH, non-tumor controls), or medulloblastoma (MB, unrelated tumoral controls) patients. 3072 proteins were identified, 47.1%, 65.6%, and 86.2% of which expressed in the unprocessed total, and its microvesicle (Mv), and exosome (Ex) fractions. Bioinformatics identified 50 statistically significant proteins in the comparison between PA and HC, and PA and MB patients, in the same fractions. Kinase enrichment analysis predicted five enriched kinases involved in signaling. Among these, only Cyclin-dependent kinase 2 (CDK2) kinase was overexpressed in PA samples. PLS-DA highlighted inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western Blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers to discriminate among pilocytic astrocytoma, and unrelated tumoral (MB) or non-tumoral conditions, in all the fractions examined, proposed to be prospectively validated in the plasma for translational medicine applications.
2024-05-23 | PXD050589 | Pride
Project description:Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. In summary, Pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.
2023-10-24 | PXD035773 | Pride
Project description:Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. In summary, pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.
2023-09-20 | GSE210353 | GEO
Project description:We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, histological subtypes as well as BRAF genetic status We also compared molecular differences to normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain expression. We analyzed the expression of 6,100 genes among 151 FFPE pediatric and 15 FFPE adult low-grade gliomas and analyzed how the expression patterns changes with location, age, histology and BRAF genomic status and how those differences were mirrored in normal brain expression. The values in the sample 'characteristics' columns represent; Location; SUP= Supratentorial, INF= Infratentorial Histology; PA= pilocytic astrocytoma, GG= ganglioglioma, DNT= dysembryoplastic neuroepithelial tumor, OD= oligodendroglial tumors, NOS= not otherwise specified tumors BRAF status; DUP= BRAF duplication, MUT= BRAF V600E mutation, WT= wild type, ND= not determined Primary or recurrent tumor; P=primary, R=recurrent Primary tumor that further progressed; 1=yes, 0=no, _=recurrent tumors only
2014-08-29 | E-GEOD-60898 | biostudies-arrayexpress