Relative spatial homogeneity revealed by transcriptional profiling of multi-region medulloblastoma samples
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE62803 | GEO | 2015/12/31
SECONDARY ACCESSION(S): PRJNA265186
REPOSITORIES: GEO
Similar Datasets
Project description:Affymetrix Human Gene 1.1 ST Array profiling of 52 primary, multi-region medulloblastoma samples. Total RNA was extracted from primary medulloblastoma samples and hybridized to Affymetrix Human Gene 1.1 ST Arrays (24-Array Plates) according to the manufacturer's instructions.
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Project description:Affymetrix Human Gene 1.1 ST Array profiling of 285 primary medulloblastoma samples. Total RNA was extracted from primary medulloblastoma samples and hybridized to Affymetrix Human Gene 1.1 ST Arrays (24-Array Plates) according to the manufacturer's instructions.
2012-07-26 | E-GEOD-37382 | biostudies-arrayexpress
Project description:Affymetrix Human Gene 1.1 ST Array profiling of 83 primary SHH-driven medulloblastoma samples.
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Project description:Affymetrix Human Gene 1.1 ST Array profiling of 83 primary SHH-driven medulloblastoma samples. Total RNA was extracted from primary medulloblastoma samples and hybridized to Affymetrix Human Gene 1.1 ST Arrays (24-Array Plates) according to the manufacturer's instructions.
2015-12-31 | E-GEOD-50765 | biostudies-arrayexpress
Project description:Affimetrix Human Gene 1.1 ST Array profiling of 763 primary medullobalstoma samples used for identification of Medullobastoma subtypes
2017-06-13 | GSE85217 | GEO
Project description:<p>Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children's Research Hospital. We have found several novel mutations which appear subtype specific. These mutations were checked for frequency in a separate tumor cohort of 56 children with medulloblastoma, also treated on the St. Jude Medulloblastoma 2003 trial, and were tested in several animal models of medulloblastoma for proof of oncogenic potential.</p>
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Project description:Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array profiling of 20 primary, multi-region high-grade glioma samples. Total RNA was extracted from primary high-grade glioma samples and hybridized to GeneChip® Human Genome U133 Plus 2.0 Array according to the manufacturer's instructions.
2015-12-31 | E-GEOD-62802 | biostudies-arrayexpress
Project description:Medulloblastoma (MB) is a brain cancer predominantly arising in children. Roughly 70% of patients are cured today, but survivors often suffer from severe sequelae. MB has been extensively studied by molecular profiling, but often in small and scattered cohorts. To improve cure rates and reduce treatment side effects, accurate integration of such data to increase analytical power will be important, if not essential. We have integrated 23 transcription datasets, spanning 1350 MB and 291 normal brain samples. To remove batch effects, we combined the Removal of Unwanted Variation (RUV) method with a novel pipeline for determining empirical negative control genes and a panel of metrics to evaluate normalization performance. The documented approach enabled the removal of a majority of batch effects, producing a large-scale, integrative dataset of MB and cerebellar expression data. The proposed strategy will be broadly applicable for accurate integration of data and incorporation of normal reference samples for studies of various diseases. We hope that the integrated dataset will improve current research in the field of MB by allowing more large-scale gene expression analyses. For all selected samples, raw CEL files were downloaded from GEO or AE. Subsequently, all raw CEL files from the same platform were processed together using the R/Bioconductor package oligo in conjunction with the RMA algorithm. The Human Gene 1.0 ST and Human Gene 1.1 ST arrays were analysed at the core level, while the Human Exon 1.0 ST arrays were processed at the extended level. Subsequently, we mapped the identifiers of the HG-U133 Plus 2 and Human Exon 1.0 ST to Human Gene 1.0/1.1 ST identifiers using `Best Match' information from Affymetrix (https://www.affymetrix.com/support/technical/byproduct.affx?product=hugene-1_0-st-v1). In addition, to increase the overlap between the Human Exon 1.0 ST and Human Gene 1.0/1.1 ST data we also inspected and added probe mappings from the `Good Match' and `Complex Match' files, including probes for the genes MYCN, PTCH1, NPR3, UNC5D, DKK2, and GABRA5. After mapping of probe identifiers within each platform, multiple rows mapping to the same identifier were collapsed using the mean value. Subsequently, all platform datasets were merged on probe identifiers, and gene symbols were assigned using the hugene11sttranscriptcluster.db package. Multiple rows mapping to the same gene or multiple columns mapping to the same patient were collapsed using the mean value. Finally, the resulting gene expression matrix was quantile normalized using the respective function in the preprocessCore package.
2019-02-06 | GSE124814 | GEO
Project description:Medulloblastoma, the most common malignant pediatric brain tumor, is highly heterogeneous with distinct molecular subtypes and cellular origins. Although current treatments improve survival rates, patients suffer severe treatment-related side effects and often relapse of tumors carrying resistance mutations, underscoring an urgent need for alternative targeted therapies. Currently, the genetic alterations underlying this disease are not fully understood. Here we identify GNAS, encoding the G-protein Gs-alpha, as a potent tumor suppressor gene in medulloblastoma. GNAS specifically defines a subset of aggressive Sonic Hedgehog (Shh)-group medulloblastomas. Gnas loss-of-function in distinct lineage progenitors of the developing hindbrain suffices to initiate medulloblastoma. We find that Gs-alpha is highly enriched at primary cilia of granule neuron precursors and suppresses Shh signaling not only by regulating classic cAMP-dependent pathway but also controlling ciliary trafficking of Smoothened. Concurrent cAMP elevation and Smoothened inhibition robustly arrests tumor cell growth in Gnas mutants. We further reveal oligodendrocyte progenitors as a novel cellular origin for anatomically-distinct Shh-associated medulloblastomas. Together, we identify a previously unrecognized tumor suppressor function of Gs-alpha in medulloblastoma partially mediated through inhibiting Shh signaling, and uncover Gs-alpha as a molecular link across disparate cells of origin among Shh-group medulloblastomas, pointing to G- protein modulation as a potential therapeutic avenue. Transgenic medulloblastoma mouse models were analyzed by Affymetrix Mouse Gene 1.1 ST Array in order to determine their molecular subgroup.
2014-08-24 | GSE60417 | GEO