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GSE26966
Homo sapiens
22 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gonadotrope or null cell pituitary tumors present clinically with signs of hypogonadism and hypopituitarism, together with visual disturbances due to mass effects. Since there are no medical therapies, surgery and/or radiation are the only therapeutic options. To identify dysregulated genes and/or pathways that may play a role in tumorigenesis and/ or progression, molecular profiling was performed on 14 gonadotrope tumors and 9 normal human pituitaries from autopsy samples. Principle component analysis (PCA) revealed clear discrimination between tumor and normal pituitary gene expression profiles. Bioinformatic analysis identified specific genes and pathways that were highly differentially regulated, including a cohort of putative downstream effectors of p53 were repressed in gonadotrope pituitary tumors, including GADD45, GADD45 and Reprimo with concomitant downregulation of the upstream regulator, PLAGL1. PLAGL1 reexpression in gonadotrope cells did not directly modulate the downstream targets. Further functional analysis of GADD45 was performed. Overexpression of GADD45 in mouse gonadotrope cells blocked proliferation, increased rates of apoptosis in response to growth factor withdrawal and increased colony formation in soft agar. In contrast to prior studies with GADD45, methylation interference assays showed no evidence of epigenetic modification of the GADD45 promoter in pituitary tumors. Thus, our data suggest that many components downstream of p53 are suppressed in gonadotrope pituitary tumors. A novel candidate, GADD45 is low in tumors and reexpression blocks proliferation, survival and tumorigenesis in gonadotrope cells. Unlike GADD45, GADD45 is not methylated to block its expression. Together these studies identify new targets and mechanisms to explore concerning pituitary tumor initiation and progression.
Publication Title
Identification of growth arrest and DNA-damage-inducible gene beta (GADD45beta) as a novel tumor suppressor in pituitary gonadotrope tumors.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 79 Downloadable Samples
Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 57 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Purpose: The incidence of malignant melanoma is increasing worldwide in fair-skinned populations. Melanomas respond poorly to systemic therapy, and metastatic melanomas inevitably become fatal. Although spontaneous regression, likely due to immune defense activation, rarely occurs, we lack a biological rationale and predictive markers in selecting patients for immune therapy. Experimental Design: We performed unsupervised hierarchical clustering of global gene expression data from stage IV melanomas in 57 patients. For further characterization, we used immunohistochemistry of selected markers, genome-wide DNA copy number analysis, genetic and epigenetic analysis of the Q3 CDKN2A locus, and NRAS/BRAF mutation screening. Results: The analysis revealed four distinct subtypes with gene signatures characterized by expression of immune response, pigmentation differentiation, proliferation, or stromal composition genes. Although all subtypes harbored NRAS and BRAF mutations, there was a significant difference between subtypes (P < 0.01), with no BRAF/NRAS wild-type samples in the proliferative subtype. Additionally, the proliferative subtype was characterized by a high frequency of CDKN2A homozygous deletions (P < 0.01). We observed a different prognosis between the subtypes (P = 0.01), with a particularly poor survival for patients harboring tumors of the proliferative subtype compared with the others (P = 0.003). Importantly, the clinical relevance of the subtypes was validated in an independent cohort of 44 stage III and IV melanomas. Moreover, low expression of an a priori defined gene set associated with immune response signaling was significantly associated with poor outcome (P = 0.001). Conclusions: Our data reveal a biologically based taxonomy of malignant melanomas with prognostic effect and support an influence of the antitumoral immune response on outcome.
Publication Title
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Purpose: The incidence of malignant melanoma is increasing worldwide in fair-skinned populations. Melanomas respond poorly to systemic therapy, and metastatic melanomas inevitably become fatal. Although spontaneous regression, likely due to immune defense activation, rarely occurs, we lack a biological rationale and predictive markers in selecting patients for immune therapy. Experimental Design: We performed unsupervised hierarchical clustering of global gene expression data from stage IV melanomas in 57 patients. For further characterization, we used immunohistochemistry of selected markers, genome-wide DNA copy number analysis, genetic and epigenetic analysis of the Q3 CDKN2A locus, and NRAS/BRAF mutation screening. Results: The analysis revealed four distinct subtypes with gene signatures characterized by expression of immune response, pigmentation differentiation, proliferation, or stromal composition genes. Although all subtypes harbored NRAS and BRAF mutations, there was a significant difference between subtypes (P < 0.01), with no BRAF/NRAS wild-type samples in the proliferative subtype. Additionally, the proliferative subtype was characterized by a high frequency of CDKN2A homozygous deletions (P < 0.01). We observed a different prognosis between the subtypes (P = 0.01), with a particularly poor survival for patients harboring tumors of the proliferative subtype compared with the others (P = 0.003). Importantly, the clinical relevance of the subtypes was validated in an independent cohort of 44 stage III and IV melanomas. Moreover, low expression of an a priori defined gene set associated with immune response signaling was significantly associated with poor outcome (P = 0.001). Conclusions: Our data reveal a biologically based taxonomy of malignant melanomas with prognostic effect and support an influence of the antitumoral immune response on outcome.
Publication Title
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have shown that removal of Lkb1 in chondorcytes results in enchondroma-like structure in postnatal mouse long bones. To furhter understand the role of Lkb1 in this process, we performed microarrrays to compare the transcriptional profile between control and conditional Lkb1 mutant (Col2a1-Cre; Lkb1c/c) chondrocytes.
Publication Title
Lkb1/Stk11 regulation of mTOR signaling controls the transition of chondrocyte fates and suppresses skeletal tumor formation.
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa
- 15 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Biofilm formation and type III secretion have been shown to be reciprocally regulated in P. aeruginosa, and it has been suggested that factors related to acute infection may be incompatible
Publication Title
Biofilms and type III secretion are not mutually exclusive in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This series includes the four major subtypes of pituitary adenomas and normal post-mortem pituitary tissue
Publication Title
Differential gene expression in pituitary adenomas by oligonucleotide array analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This sample is part of a study that compares small sample amplification technologies. The analysis looks at differential gene expression when compared to one round of T7 amplification. A tumor cell line was used in comparison to a human reference RNA in this study.
Publication Title
Big results from small samples: evaluation of amplification protocols for gene expression profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
In this study we have investigated the effect of loss of math-33 activity on DAF-16-mediated target gene regulation in C. elegans under conditions of reduced Insulin/IGF-1 signaling (IIS). Using whole nematode RNA sequencing experiments we found that the daf-2(e1370)-mediated induction and repression of DAF-16 target genes was decreased in daf-2(e1370); math-33(tm3561) mutant animals. Our data suggest that the downregulation of endogenous DAF-16 isoforms in the absence of a functional MATH-33 severely affects the global expression of DAF-16 targets when IIS activity is reduced. Therefore, MATH-33 is essential for DAF-16-mediated target gene activation and repression in the context of IIS. Overall design: DAF-16 mediated target gene regulation was analyzed in daf-2(e1370) nematodes and compared to daf-2(e1370); math-33(tm3561) mutant animals. daf-16(mu86); daf-2(e1370); N2 (wild type) and math-33(tm3561) single mutant animals were used as controls.
Publication Title
The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Allergen exposure induces the airway epithelium to produce chemoattractants, proallergic interleukins, matrix-modifying proteins, and proteins that influence the growth and activation state of airway structural cells. These proteins, in turn, contribute to the influx of inflammatory cells and changes in structure that characterize the asthmatic airway. To use the response of the airway epithelium to allergen to identify genes not previously associated with allergic responses, we compared gene expression in cytokeratin-positive cells before and after segmental allergen challenge. After challenge with concentrations of allergen in the clinically relevant range, 755 (6%) of the detectable sequences had geometric mean fold-changes in expression, with 95% confidence intervals that excluded unity. Using a prospectively defined conservative filtering algorithm, we identified 141 sequences as upregulated and eight as downregulated, with confirmation by conventional polymerase chain reaction in all 10 sequences studied. Using this approach, we identified asthma-associated sequences including interleukin (IL-)-3, IL-4, and IL-5 receptor subunits, the p65 component of nuclear factor-kappaB, and lipocortin. The genomic response of the human airway to concentrations of allergen in the clinically relevant range involves a greater number of genes than previously recognized, including many not previously associated with asthma that are differentially expressed after airway allergen exposure.
Publication Title
Effects of allergen challenge on airway epithelial cell gene expression.
Sample Metadata Fields
No sample metadata fields
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