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GSE12992
Homo sapiens
39 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Medulloblastoma is the most frequent malignant pediatric brain tumor. Considerable efforts are dedicated to identify markers that help to refine treatment strategies. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favorable patient outcome. We report a series of 72 pediatric medulloblastomas evaluated for beta-catenin immunostaining, CTNNB1 mutations, and studied by comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumor cells) in 6 cases and focal nuclear staining (<10% of cells) in 3 cases. The other cases exhibited either a signal strictly limited to the cytoplasm (58 cases) or were negative (5 cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented a strong activation of the Wnt/beta-catenin pathway. Remarkably, 5 out of these 6 tumors showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumors with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2) from diagnosis. All three patients with a focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumors represent a distinct molecular subgroup of medulloblastomas with favorable outcome, indicating that therapy de-escalation should be considered. Yet, international consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved.
Publication Title
Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Pediatric medulloblastoma is considered a highly heterogeneous disease, and a new strategy of risk stratification to optimize therapeutic outcomes is required. We aimed to investigate a new risk-stratification approach based on expression profiles of medulloblastoma cohorts. We analyzed gene expression profiles of 30 primary medulloblastomas and detected strong evidence that poor survival outcome was significantly associated with mRNA expression profiles of 17p loss. However, it was not supported in independent cohorts from previously published data (n=100). We speculated that this controversy might come from complex conditions of two important prognostic determinants, loss of tumor suppressors (chromosome 17p) and high expression of oncogenes, c-myc (MYC) or N-myc (MYCN). Simultaneous consideration of these two factors led to a new subgrouping of patients, exhibiting obviously different survival expectancies between the subgroups. Patients with up-regulated WNT signalings were always pre-defined as an independent subgroup, which ultimately removed confounding effect arising from contradictory outcome, favorable prognosis of WNT medulloblastomas despite their high MYC/MYCN expression level. We also found that age is a significant prognostic marker after adjusting for 17p and MYC/MYCN status. Diminished survival in age <3 years was more substantial in groups with high expression of MYC/MYCN or 17p loss, indicating survival outcome might be coordinately affected by these three factors. We suggest a more tailored and easily applicable subgrouping system based on expression profiles of chromosome 17p and MYC/MYCN, while separating WNT medulloblastoma as an independent subgroup, which could provide the basis for a novel risk-stratification strategy in pediatric medulloblastoma.
Publication Title
Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of MYCC and MYCN, and Wnt pathway activation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
RNA helicases DDX5 and DDX17 are members of a large family of highly conserved proteins involved in gene expression regulation, although their in vivo targets and activities in biological processes like cell differentiation, that requires reprogramming of gene expression programs at multiple levels, are not well characterized. In this report, we uncovered a new mechanism by which DDX5 and DDX17 cooperate with hnRNP H/F splicing factors to define epithelial- and myoblast-specific splicing subprograms. We next observed that downregulation of DDX5 and DDX17 protein expression during epithelial to mesenchymal transdifferentiation and during myogenesis contributes to switching splicing programs during these processes. Remarkably, this downregulation is mediated by the production of microRNAs induced upon differentiation in a DDX5/DDX17-dependent manner. Since DDX5 and DDX17 also function as coregulators of master transcriptional regulators of differentiation, we propose to name these proteins master orchestrators of differentiation, that dynamically orchestrate several layers of gene expression.
Publication Title
RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
IlluminaHiSeq2500
Description
Familial Dysautonomia is a genetic disease, however patietns with the same genotype present with mild or severe forms of the disease. We used the pluripotent stem cell technology to capture the differences in disease severity in vitro during neurodevelopment as well as during maintanance of the cells, showing developmental and degenerative phenotypes. RNA seq. analysis of the groups confirmed those diffferences. Overall design: Analysis of RNA from PSC-derived neural crest cells from severe FD, mild FD and healthy patients
Publication Title
Capturing the biology of disease severity in a PSC-based model of familial dysautonomia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
We have generated expression profiles of induced pluripotent stem cells (iPSCs) and iPSC-derived neural crest populations from Familial Dysautonomia patients. These profiles were compared to a normal iPSC line that does not harbor the IKBKAP mutation. Overall design: All cell types were differentiated from patient derived iPSCs. Bulk iPSCs were harvested for RNA and the neural crest populations were sorted on day 18 for p75/HNK1 before RNA isolation.
Publication Title
Capturing the biology of disease severity in a PSC-based model of familial dysautonomia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
Mitochondrial biogenesis and metabolism recently emerged as critical modulators of stemness properties and differentiation programmes. The increase in mitochondrial biogenesis and metabolic shift toward increased oxidative phosphorylations (OXPHOS) appear as hallmarks of stem cell differentiation processes. While several mechanisms support the involvement of mitochondrial biogenesis and function in the regulation of stem cell differentiation, the mechanisms triggering mitochondrial biogenesis in the context of cell differentiation remain elusive. In this study, we performed transcriptomic and bioinformatic analyses in order to get deeper insights into the cross-regulation of mitochondrial biogenesis and hepatogenic differentiation of human bone marrow mesenchymal stem cells (BM-MSCs). We identified a transcriptional regulatory network involved in the co-regulation of stem cell differentiation and mitochondrial biogenesis. Overall design: Transcriptomics analyses performed at early time points of the hepatogenic differentiation of BM-MSC
Publication Title
MPV17 does not control cancer cell proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 40 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Keap1/Nrf2 signaling pathway is a tractable target for the pharmacological prevention of tumorigenesis. 3H-1,2-dithiole-3-thione (D3T) and 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) are representative members of two classes of Nrf2-activating chemopreventive agents. Natural dithiolethiones have been widely used in clinical trials for cancer chemoprevention. Synthetic triterpenoids, however, have been shown to be significantly more potent Nrf2 activators and are under clinical evaluation for the treatment of chronic kidney disease. This study seeks to characterize the structure-activity relationship between D3T and CDDO-Im in mouse liver tissue. To this end we treated Wt and Nrf2-null mice with 300 umol/kg bw D3T and 3, 10, and 30 umol/kg bw CDDO-Im every other day for 5 days and evaulated global gene expression changes as a product of both treamtent and genotype using Affymetrix microarray.
Publication Title
Pharmacogenomics of Chemically Distinct Classes of Keap1-Nrf2 Activators Identify Common and Unique Gene, Protein, and Pathway Responses In Vivo.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 137 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The purpose of this study was to characterize the transcriptional effects induced by intramuscular IFN-beta-1a treatment (Avonex, 30 g once weekly) in patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of peripheral blood mononuclear cells from 24 MS patients within the first four weeks of IFN-beta administration.
Publication Title
Network analysis of transcriptional regulation in response to intramuscular interferon-β-1a multiple sclerosis treatment.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Disseminated prostate cancer cells colonize the skeleton to progress into macroscopic lesions only if they successfully adapt to the bone microenvironment. We previously reported that the ability of prostate cancer cells to generate skeletal tumors in animal models correlated with the expression of the alpha-receptor for Platelet-Derived Growth Factor (PDGFRa). In this study we aimed to identify PDGFRa-regulated genes responsible for the acquisition of a bone-metastatic prostate phenotype. We performed genome-wide expression comparative analyses of human prostate cancer cell lines that differ for PDGFRa expression and propensity to establish tumors in the skeleton of animal models. We investigated the genes that were differentially regulated in the highly bone-metastatic PC3-ML cells and their low-metastatic counterpart PC3-N cells, and the genes differentially regulated between PC3-N and PC3-N with overexpression of PDGFRa (PC3NRa). We have previously shown that DU-145 cells lack PDGFRa and fail to survive longer than three days as disseminated tumor cells after homing to the mouse bone marrow. Interestingly, and in contrast to PC3-N cells, the exogenous expression of PDGFRa did not promote metastatic bone-tropism of DU-145 cells in our model. Thus, we examined the genes that were differentially regulated between DU-145 and DU-145(Ra) and excluded them from our candidate genes. Finally, to refine our findings and compensate for PC3 and DU-145 genetic disparity, we performed a comparative analysis of the genes differentially regulated between two bone metastatic single-cell progenies that were derived from PC3-ML cells.
Publication Title
Interleukin-1β promotes skeletal colonization and progression of metastatic prostate cancer cells with neuroendocrine features.
Sample Metadata Fields
Cell line
View Samples- Escherichia coli
- 6 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Transcriptional profiles of uropathogenic Escherichia coli CFT073 exposed to cranberry-derived proanthocyanidins (PACs) were determined. Our results indicate that bacteria grown on media supplemented with PACs were iron-deprived. To our knowledge, this is the first time that PACs have been shown to induce a state of iron-limitation in this bacterium.
Publication Title
Induction of a state of iron limitation in uropathogenic Escherichia coli CFT073 by cranberry-derived proanthocyanidins as revealed by microarray analysis.
Sample Metadata Fields
No sample metadata fields
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