Gene expression of LMPC cells of infratentorial ependymomas when compared to LMPC ependymal cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE25604 | GEO | 2010/12/10
SECONDARY ACCESSION(S): PRJNA134249
REPOSITORIES: GEO
Similar Datasets
Project description:Ependymomas are glial tumors that share morphologic similarities with ependymal cells. Here we laser microdissected ependymoma cells of 15 infratentorial tumors and generated gene expression profiles. These profiles were compared to those of 7 laser microdissected ependymal tissues. 10 000 laser microdissected cells of each of the 15 different infratentorial ependymomas and seven ependymal autopsy tissues were lysed and gene expression profiles were generated. Expression profiles of ependymomas were compared to those of ependymal cells.
2010-12-10 | E-GEOD-25604 | biostudies-arrayexpress
Project description:Genomic technologies have unmasked molecularly distinct subgroups among tumors of the same histological type; but understanding the biologic basis of these subgroups has proved difficult since their defining alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher complex genomic data sets by matching the genetic alterations contained within these, with candidate cells of origin, to generate accurate disease models. Using an integrated genomic analysis we first identified subgroups of human ependymoma: a form of neural tumor that arises throughout the central nervous system (CNS). Validated alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. Matching the transcriptomes of human ependymoma subgroups to those of distinct types of mouse radial glia (RG)—neural stem cells (NSCs) that we identified previously to be a candidate cell of origin of ependymoma - allowed us to select RG types most likely to represent cells of origin of disease subgroups. The transcriptome of human cerebral ependymomas that amplify EPHB2 and delete INK4A/ARF matched most closely that of embryonic cerebral Ink4a/Arf-/- RG: remarkably, activation of EphB2 signaling in this RG type, but not others, generated highly penetrant ependymomas that modeled accurately the histology and transcriptome of one human cerebral tumor subgroup (subgroup ‘D’). Further comparative genomic analysis revealed selective alterations in the copy number and expression of genes that regulate neural differentiation, particularly synaptogenesis, in both mouse and human subgroup ‘D’ ependymomas; pinpointing this pathway as a previously unknown target of ependymoma tumorigenesis. Our data demonstrate the power of comparative genomics to sift complex genetic data sets to identify key molecular alterations in cancer subgroups. [human mRNA] samples: 83 human ependynoma primary tumors were collected and clustered into distinct classes by unsupervised methods and then compared to mouse model data. [mouse mRNA] samples: 192 mouse tumors and cell lines were collected and clustered into distinct classes by unsupervised methods and then compared to human tumors. [human miRNA] samples: 64 human ependynoma primary tumors were collected and miRNA expression was assesed and compared to genomic expression
2010-07-19 | E-GEOD-21687 | biostudies-arrayexpress
Project description:Ependymal tumors across age groups have been classified solely by histopathology. It is, however, commonly accepted that this classification has limited clinical utility based on its poor reliability. We aimed at establishing a reliable and reproducible molecular classification using DNA methylation fingerprints of the tumors. Studying a cohort of 500 tumors allowed for the delineation of nine robust molecular subgroups, three in each anatomic compartment of the central nervous system (CNS). Two of the supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification by far and thus might serve as a basis for the upcoming update of the WHO classification of CNS tumors. DNA methylation patterns in tumors have been shown to represent a very stable molecular memory of the respective cell of origin throughout the disease course, thus making them particularly suitable for tumor classification purposes. Methylation fingerprinting of a large series of ependymal tumors of all grades revealed a highly reliable way of classifying this clinically extremely heterogeneous group of malignancies. In fact, out of nine highly reproducible molecular subgroups identified in the supratentorial, infratentorial and spinal regions, only two harbor the vast majority of clinical high-risk patients (mostly children) for whom novel therapeutic concepts are desperately needed. Since this analysis can be performed from minute amounts of DNA extracted from archived material, it is ideally suited for routine clinical application. We investigated a set of 562 ependymal tumors using the Illumina 450k methylation array.
2015-05-21 | E-GEOD-65362 | biostudies-arrayexpress
Project description:Adult human ependymal and ventral horn regions were obtained from postmortem frozen samples by Laser Capture Microdissection. Briefly, Cryostat 25 micron sections from were stained with toluidin blue and both regions microdissected and collected on eppendorf (n=4 for each region). Samples mRNA concentration and purity was assessed by electrophoresis (BioRad Experion HighSensitivity kit, USA). RQI values were lower than 6,5 in every case, so that purification was followed by 2 cycle amplification with a kit designed for highly degraded samples (ExpressArt® TRinucleotide mRNA Amplification Kit; #6299-A15, AmpTec, AMSBIO, UK). After amplification, mRNA concentration and purity was assessed both by electrophoresis (BioRad Experion StSens kit, USA) and by spectrophotometry (Nanodrop, Thermo Scientific, USA). We amplified 3.7-37 ng of total RNA, obtaining between 6 and 21 µg of mRNA after 2 rounds. After collecting samples and studying the RNA integrity and quantity, cDNA of samples was selected for gene expression assays using 384 wells Custom Taqman Low Density Arrays. We built arrays with genes belonging to a profile of stemness or ependymoma (see Garcia-Ovejero et al., 2015, BRAIN). Taqman based qPCR gene expression profiling. Ependymal and ventral horn regions obtained by LCMD from four different individuals each were used to establish genes involved in stem cell niches or in ependymoma phenotype that are enriched in control human ependyma using ventral horn as a non-ependymary, non-neurogenic region. Samples were treated as stated in the summary. Equal amount of amplified RNA (aRNA; 25ng, corresponding approximately to 500ng total RNA) from each donor was used in Custom Designed Taqman Low Density Arrays. Every value is the resultant of duplicates at least, but most of them have been assayed 4 times.
2015-04-12 | E-GEOD-65463 | biostudies-arrayexpress
Project description:Gene expression (mRNA) profiling of human ependymomas Despite the histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymoma. Group-A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, secondary metastasis, and death as compared to Group-B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third independent group of tumors using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. We analyzed 102 primary ependymomas on the Affymetrix Exon 1.0ST platform (Gene Level).
2011-08-14 | E-GEOD-27279 | biostudies-arrayexpress
Project description:Adult human ependymal and ventral horn regions were obtained from postmortem frozen samples by Laser Capture Microdissection. Briefly, Cryostat 25 micron sections from were stained with toluidin blue and both regions microdissected and collected on eppendorf (n=4 for each region). Samples mRNA concentration and purity was assessed by electrophoresis (BioRad Experion HighSensitivity kit, USA). RQI values were lower than 6,5 in every case, so that purification was followed by 2 cycle amplification with a kit designed for highly degraded samples (ExpressArt® TRinucleotide mRNA Amplification Kit; #6299-A15, AmpTec, AMSBIO, UK). After amplification, mRNA concentration and purity was assessed both by electrophoresis (BioRad Experion StSens kit, USA) and by spectrophotometry (Nanodrop, Thermo Scientific, USA). We amplified 3.7-37 ng of total RNA, obtaining between 6 and 21 µg of mRNA after 2 rounds. After collecting samples and studying the RNA integrity and quantity, cDNA of samples was selected for gene expression assays using 384 wells Custom Taqman Low Density Arrays. We built arrays with genes belonging to a profile of stemness or ependymoma (see Garcia-Ovejero et al., 2015, BRAIN).
2015-04-12 | GSE65463 | GEO
Project description:The spinal cord neural stem cell potential is contained within the ependymal cells lining the central canal. Ependymal cells are, however, heterogeneous and we know little about what this reflects. To gain new insights into ependymal cell heterogeneity, we microdissected the ependymal cell layer from the thoracic spinal cord of 4 FOXJ1-EGFP transgenic mice (2.5-to-3-month old). After after dissociating the tissue into a cell suspension, we sorted single GFP-positive ependymal cells into lysis plates. cDNA synthesis was performed using Smart-seq2 technology.
2022-12-13 | E-MTAB-11563 | biostudies-arrayexpress
Project description:Despite histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymomas reveals the existence of two demographically, transcriptionally, genetically and clinically distinct groups of posterior fossa (PF) ependymoma. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis, and death as compared to Group B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third group of independent ependymomas using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. This SuperSeries is composed of the following subset Series: GSE27283: Human ependymoma samples [expression] GSE27286: Human ependymoma samples, Subgrouping [aCGH - German Cancer Research Center human 33K BAC array] Refer to individual Series
2011-08-14 | E-GEOD-27287 | biostudies-arrayexpress
Project description:FoxJ1 dependent gene expression is required for establishment of ependymal cells in the postnatal brain. This data set compares gene expression profiles of wildtype and FoxJ1 null microdissected dissected tissues at multiple postnatal time points. We used microarrays to detail the FoxJ1-dependent programme of gene expression underlying ependymal cell differentiation in the mouse brain.
2009-10-21 | GSE18678 | GEO
Project description:Background: A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas. Methods: Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from eight diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were retrospectively correlated with progression-free survival (PFS). Results: The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6% and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (p=0.009) and postoperative radiotherapy (p=0.007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of prognosis within molecularly defined ependymoma classes. Conclusions: DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. Gross total resection and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.
2023-02-21 | GSE224218 | GEO