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GSE9339
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neuroblastoma is an embryonal tumour of the peripheral sympathetic nervous system (SNS). One of the master regulator genes for peripheral SNS differentiation, the homeobox transcription factor PHOX2B, is mutated in familiar and sporadic neuroblastomas. Here we report that inducible expression of PHOX2B in the neuroblastoma cell line SJNB-8 down-regulates MSX1, a homeobox gene important for embryonic neural crest development. Inducible expression of MSX1 in SJNB-8 caused inhibition of both cell proliferation and colony formation in soft agar. Affymetrix micro- array and Northern blot analysis demonstrated that MSX1 strongly up-regulated the Delta-Notch pathway. These experiments describe for the first time regulation of the Delta-Notch pathway by MSX1, and connect these genes to the PHOX2B oncogene, indicative of a role in neuroblastoma biology.
Publication Title
The MSX1 homeobox transcription factor is a downstream target of PHOX2B and activates the Delta-Notch pathway in neuroblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations affecting the RAS-MAPK pathway frequently occur in relapse neuroblastoma tumors, which suggests that activation of this pathway is associated with a more aggressive phenotype. To explore this hypothesis we generated several model systems to define a neuroblastoma RAS-MAPK pathway signature. We could show that activation of this pathway in primary tumors indeed correlates with poor survival and is associated with known activating mutations in ALK and other RAS-MAPK pathway genes. From integrative analysis we could show that mutations in PHOX2B, CIC and DMD are also associated with an activated RAS-MAPK pathway. Mutation of PHOX2B and deletion of CIC in neuroblastoma cell lines induces activation of the RAS-MAPK pathway. This activation was independent of phosphorylated ERK in the CIC knock out systems. Furthermore, deletion of CIC causes a significant increase in tumor growth in vivo. These results show that the RAS-MAPK pathway is involved in tumor progression, and establish CIC as a powerful tumor suppressor that functions downstream of this pathway in neuroblastoma.
Publication Title
RAS-MAPK Pathway-Driven Tumor Progression Is Associated with Loss of CIC and Other Genomic Aberrations in Neuroblastoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Whole genome sequencing detected structural rearrangements of TERT in 17/75 high stage neuroblastoma with 5 cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted immediate up- and down-stream regions of TERT, placing in 7 cases a super-enhancer close to the breakpoints. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high stage neuroblastoma, each associated with very poor prognosis
Publication Title
TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Wilms tumor (nephroblastoma) is a pediatric kidney tumor that arises from renal progenitor cells. Since the blastemal type is associated with adverse prognosis, we characterized such Wilms tumors by exome and transcriptome analysis. We detected novel, recurrent somatic mutations affecting the SIX1/2 SALL1 pathway implicated in kidney development, the DROSHA/DGCR8 microprocessor genes as well as alterations in MYCN and TP53, the latter being strongly associated with dismal outcome. The DROSHA mutations impair the RNase III domains, while DGCR8 exhibits stereotypic E518K mutations in the RNA binding domain - both may skew miRNA representation. SIX1 and SIX2 mutations affect a single hotspot (Q177R) in the homeodomain indicative of a dominant effect. In larger cohorts, these mutations cluster in blastemal and chemotherapy-induced regressive tumors that likely derive from blastemal cells and these are characterized by generally higher SIX1/2 expression. These findings broaden the spectrum of human cancer genes and may open new avenues for stratification and therapeutic leads for Wilms tumors.
Publication Title
Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We present a microarray analysis of primary mouse astrocytes exposed to HIV-1 in culture. Results are compared with previous genomic studies of HIV-1 effect in human astrocytes and human and macaque brains.
Publication Title
Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal (CRC) patients. For most, organoids were also generated from adjacent normal tissue. The organoids closely resemble the original tumor. The spectrum of genetic changes observed within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to robotized, high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43 (rather than in APC). Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design.
Publication Title
Prospective derivation of a living organoid biobank of colorectal cancer patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Drosophila melanogaster
- 3 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Mutant embryos lacking maternal and zygotic HOW exhibit defects in mesoderm development. How is an RNA binding protein that regulates the levels of mRNAs by controling RNA metabolism.
Publication Title
Post-transcriptional repression of the Drosophila midkine and pleiotrophin homolog miple by HOW is essential for correct mesoderm spreading.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The Akita mutation (C96Y) in the insulin gene results in early onset diabetes in both humans and mice. Expression of the mutant proinsulin (C96Y) causes endoplasmic reticulum (ER) stress in pancreatic -cells and consequently the cell activates the unfolded protein response (UPR). Since the proinsulin is terminally misfolded however, the ER stress is irremediable and chronic activation of the UPR eventually activates apoptosis in the cell population.
Publication Title
IRE1 inhibition perturbs the unfolded protein response in a pancreatic β-cell line expressing mutant proinsulin, but does not sensitize the cells to apoptosis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
A doxycyline-inducible INS-1 insulinoma cell line expressing proinsulin (C96Y)-GFP was engineered. Addition of doxycyline causes the production of the proinsulin (C96Y)-GFP, which is retained in the endoplasmic reticulum. This study analyzes the gene expression changes that occur after doxycyline-induced expression of proinsulin (C96Y)-GFP for 24h, 48h and 5 days. Expression changes were compared between control un-induced cells and cells treated with doxycyline. Three replicates (experiments) were performed for each time point.
Publication Title
Endoplasmic reticulum stress response in an INS-1 pancreatic beta-cell line with inducible expression of a folding-deficient proinsulin.
Sample Metadata Fields
Cell line
View Samples