Gene Expression Profiling of Human Pediatric Astrocytomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE38330 | GEO | 2012/08/24
SECONDARY ACCESSION(S): PRJNA167680
REPOSITORIES: GEO
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Project description:Analysis of grades II, II and iV pediatric astrocytomas. Results used to straify tumors into molecular subclasses representative of adult tumors. The mesenchymal subtype is associated with high expression of immune response-related genes. Gene expression of grade II, III and IV pediatric astrocytomas, 24 individual tumor samples were profiled
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Project description:Comparison of grade II astrocytic tumor (astrocytomas) with grade IV tumors (glioblastoma)
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Project description:Pediatric astrocytomas, a leading cause of death associated with cancer, are the most common primary central nervous system tumors found in children. Most studies of these tumors focus on adults, not children. We examined the global protein and microRNAs expression pattern by 2D SDS-PAGE, mass spectrometry (MALDI-TOF) and RT2 miRNA PCR Array System. MicroRNAs analysis revealed for the first time novel microRNAs involved in astrocytomas biology. Interestingly, miR-138 and miR-145 down-regulation appear to be associated with protein over-expression of vimentin and Bax, respectively. In conclusion, our results show that novel proteins and microRNAs altered on pediatric astrocytoma could serve as biomarkers to distinguish between astrocytoma grades. Astrocytoma samples were colected from patients and total RNA isolation (30 mg of tissue) was performed using the TRIzol® protocol (Invitrogen, USA) according to the manufacturer′s instructions. Samples were analyzed using SA Biosciences RT2 miRNA PCRArray System to determied the miRNA expression between control samples and tumors
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Project description:Novel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006. Experiment Overall Design: 77 primary high-grade astrocytomas and 23 matched recurrences were profiled to identify changes in gene expression that relate to both survival and disease progression. Samples include WHO grade III and IV astrocytomas with a wide range of survival times.
2007-10-02 | E-GEOD-4271 | biostudies-arrayexpress
Project description:Pediatric astrocytomas, a leading cause of death associated with cancer, are the most common primary central nervous system tumors found in children. Most studies of these tumors focus on adults, not children. We examined the global protein and microRNAs expression pattern by 2D SDS-PAGE, mass spectrometry (MALDI-TOF) and RT2 miRNA PCR Array System. MicroRNAs analysis revealed for the first time novel microRNAs involved in astrocytomas biology. Interestingly, miR-138 and miR-145 down-regulation appear to be associated with protein over-expression of vimentin and Bax, respectively. In conclusion, our results show that novel proteins and microRNAs altered on pediatric astrocytoma could serve as biomarkers to distinguish between astrocytoma grades. Astrocytoma samples were colected from patients and total RNA isolation (30 mg of tissue) was performed using the TRIzolM-BM-. protocol (Invitrogen, USA) according to the manufacturerM-bM-^@M-2s instructions. Samples were analyzed using SA Biosciences RT2 miRNA PCRArray System to determied the miRNA expression between control samples and tumors RT2 miRNA PCR Array. Eigth tumor samples and two control tissue (including two control tissue replicates) were used as indicated in the sumary. A total of 3ug of RNA from each tumr samples and control tissue were placed in the PCR Array
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Project description:We have used microarray comparative genomic hybridization (aCGH) at 1Mb resolution to study copy number changes in a series of WHO Grade II Astrocytomas (n=21). We have used Illumina arrays to study genome-wide expression patterns in a series of WHO Grade II Astrocytomas (n=10). Keywords: Array Comparative Genomic Hybridization (aCGH), Expression microarray [aCGH]: Single hybridization per case. 21 astrocytomas WHO grade II were analyzed. Target (tumor) labelled with Cy5 and reference with Cy3. Mixture of 20 normal male or female genomic DNA was used in sex-mismatched hybridization. [mRNA]: Single hybridization per case. 10 astrocytomas WHO grade II were analyzed (5 adult, 5 pediatric)
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Project description:DNA copy-number profiling of 66 astrocytomas of WHO °I or °II Keywords: Genetic modification
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Project description:Tumors of the central nervous system are the most common solid neoplasia during human childhood, representing one of the leading causes of cancer-related mortality. Tumors that originate from astrocyte cells (astrocytoma) in the brain are the most frequently found. According to their histological and pathological features, these tumors are classified into four categories. However, recently an extra layer of molecular classification of the tumorigenesis-associated genes IDH1/2 and H3F3A has been incorporated into the classification guidelines. While mutations in H3F3A are exclusively found in a subtype of pediatric astrocytoma grade IV, mutations in IDH1/2 are very rare in children younger than 14 years old. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied however focusing on the study of the transcriptomic profile of the different grades of astrocytoma (including the additional layer of molecular classification) in pediatric populations are scarce. Therefore, we have profiled the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing.
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Project description:The aim of the study was to identify significant alterations in genes and molecular functional pathways in comparison with normal and ACM tissue, and detect the marker genes to differentiate the different stage astrocytomas Total RNA was isolated from Seventeen tumor tissue of patients, which included two WHO grade I(T1) and five WHO grade II(T2), III(T3) and IV(T4) samples, and four pooled normal tissue samples. The genome-wide expression analysis was first performed by directly comparing the expression profile of highly enriched different grade astrocytomas and pooled normal tissues, we then applied various data-mining methods to process the 15 different grades tumor tissues sample. Paired T-test and Q-cluster method was performed to explore mark genes validated by qRT-PCR. This study utilized a pathway-specific enrichment analysis of the microarray data and quantified the gene expression difference between astrocytomas tumor and pooled normal tissues. BioCarta and KEGG pathways of the ACM compared to normal tissue were identified through enrichment tests on gene lists obtained using SAM, while GO is organized into hierarchical annotations in the context of normal cellular function, the BioCarta and KEGG database organizes the genes(gen products) into pathway reaction maps and functional complexes, including some disease-specific pathway
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Project description:Astrocytomas are common and lethal human brain tumors. Here, we have analyzed the methylation status of over 28,000 CpG islands and 18,000 promoters in normal human brain and in astrocytomas of various grades using the methylated-CpG island recovery assay (MIRA). We identified six to seven thousand methylated CpG islands in normal human brain. ~5% of the promoter-associated CpG islands in normal brain are methylated. Promoter CpG island methylation is inversely and intragenic methylation is directly correlated with gene expression levels in brain tissue. In astrocytomas, several hundred CpG islands undergo specific hypermethylation relative to normal brain with 428 methylation peaks common to more than 25% of the tumors. Genes involved in brain development and neuronal differentiation, such as POU4F3, GDNF, OTX2, NEFM, CNTN4, OTP, SIM1, FYN, EN1, CHAT, GSX2, NKX6-1, RAX, PAX6, DLX2, were strongly enriched among genes frequently methylated in tumors. There was an overrepresentation of homeobox genes and 31% of the most commonly methylated genes represent targets of the Polycomb complex. We identified several chromosomal loci in which many (sometimes more than 20) consecutive CpG islands were hypermethylated in tumors. Seven of such loci were near homeobox genes, including the HOXC and HOXD clusters, and the BARHL2, DLX1, and PITX2 genes. Two other clusters of hypermethylated islands were at sequences of recent gene duplication events. Our analysis offers mechanistic insights into brain neoplasia suggesting that methylation of genes involved in neuronal differentiation, perhaps in cooperation with other oncogenic events, may shift the balance from regulated differentiation towards gliomagenesis. Comparison of methylation patterns of 30 astrocytomas and 6 controls
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