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GSE76039
Homo sapiens
37 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BACKGROUND. Poorly-differentiated (PDTC) and anaplastic (ATC) thyroid cancers are rare and frequently lethal tumors, which so far have not been subjected to comprehensive genetic characterization. METHODS. We performed next generation sequencing of 341 cancer genes in 117 PDTCs and ATCs, and a transcriptomic analysis of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas (TCGA) study of papillary thyroid cancers (PTC). RESULTS. ATCs have a greater mutation burden than PDTCs, and higher mutation frequency of TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits and histone methyltransferases. BRAF and RAS are the predominant drivers, and dictate remarkably distinct tropism for nodal vs. distant metastases in PDTC. RAS and BRAF sharply distinguish between PDTCs defined by the Turin (PDTC-Turin) vs. MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, are markedly enriched in PDTCs and ATCs, and have a striking pattern of co-occurrence with RAS. TERT promoter mutations are rare and subclonal in PTCs, whereas they are clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) shows a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs are BRAF-like irrespective of driver mutation. CONCLUSIONS. These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared to PDTC underscore their greater virulence and higher mortality.
Publication Title
Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission.
Publication Title
Transcriptional analysis of the intestinal mucosa of patients with ulcerative colitis in remission reveals lasting epithelial cell alterations.
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tolerogenic dendritic cells (tol-DCs) offer a promising therapeutic potential for autoimmune diseases. Tol-DCs have been reported to inhibit immunogenic responses, yet little is known about the mechanisms controlling their tolerogenic status, as well as associated specific markers. Here we show that the anti-inflammatory TAM receptor tyrosine kinase MERTK, is highly expressed on clinical grade dexamethasone-induced human tol-DCs and mediates their tolerogenic effect. Neutralization of MERTK in allogenic mixed lymphocyte reactions as well as autologous DC-T cell cultures leads to increased T cell proliferation and IFN-g production. Additionally, we identify a previously unrecognized non-cell autonomous regulatory function of MERTK expressed on DCs. Recombinant Mer-Fc protein, used to mimic MERTK on DCs, suppresses nave and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK agonist Protein S (PROS1) expressed by T cells. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine pro-proliferative mechanism. Collectively, these results suggest that MERTK on tol-DCs directly inhibits T cell activation through the competition for PROS1 interaction with MERTK in the T cells. Targeting MERTK may provide an interesting approach to effectively increase or suppress tolerance for the purpose of immunotherapy.
Publication Title
MERTK as negative regulator of human T cell activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Crohn's Disease (CD) is a chronic inflammatory disease of the intestinal tract.
Publication Title
Identification of inflammatory mediators in patients with Crohn's disease unresponsive to anti-TNFα therapy.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Chronic inflammation leading to pro-inflammatory macrophage infiltration contributes to the pathogenesis of type 2 diabetes and subsequently the development of diabetic nephropathy. Mesenchymal stem cells (MSCs) possess unique immunomodulatory and cytoprotective properties making them an ideal candidate for therapeutic intervention
Publication Title
Human mesenchymal stem cells alter the gene profile of monocytes from patients with Type 2 diabetes and end-stage renal disease.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Astrocytes from optic nerve head from donors with and without glaucoma
Publication Title
Differential gene expression in astrocytes from human normal and glaucomatous optic nerve head analyzed by cDNA microarray.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 122 Downloadable Samples
Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aldokatoreductases (AKRs) represent a gene superfamily that code for monomeric, soluble NAD(P)H-dependent oxidoreductases that mediate elimination reactions. AKR1B10, an AKR that functions to eliminate retinals, has been observed to be upregulated in squamous metaplasma and non small cell lung cancer, and has been suggested as a diagnostic marker specific to tobacco-related carcinogenesis. In the context of the link of smoking and lung cancer and the enhanced expression of AKR1B10 expression in lung cancer, we hypothesize that enhanced expression of AKR1B10 may be initiated in healthy smokers, prior to the development of any evidence of lung cancer. For this purpose, expression of AKR1B10 was assessed at the mRNA level using microarrays in the large airway epithelium (21 healthy nonsmokers, 31 health smokers) and small airway epithelium (51 healthy nonsmokers, 58 healthy smokers) obtained by fiberoptic bronchoscopy and brushing, as well as assessment in a subset of this population by TaqMan PCR and in endobronchial biopsies by Western analysis and immunohistochemistry. Compared to healthy nonsmokers, ARK1B10 mRNA levels were markedly upregulated in both the large and small airway epithelium of healthy smokers (large airway microarray p<0.0001, small airway p<0.0001; TaqMan large airway, p<0.02, small airway p<0.01). Consistent with the mRNA data, AKR1B10 protein was significantly upregulated in the airway epithelium of healthy smokers as assessed by Western analysis and by immunohistochemistry, with AKR1B10 expressed in both differentiated and basal cells of the normal epithelium. Finally, cigarette smoke extract mediated up-regulation of AKR1B10 in airway epithelial cells in vitro. Thus, smoking per se mediates up-regulation of AKR1B10 expression in the airway epithelium of healthy smokers with no evidence of lung cancer. In the context of these observations, and the link of AKR1B10 to the metabolism of retinals and to lung cancer, the smoking-induced up-regulation of AKR1B10 may be an early process in the multiple events leading to the develop of lung cancer.
Publication Title
Smoking-induced upregulation of AKR1B10 expression in the airway epithelium of healthy individuals.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 95 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission.
Publication Title
Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Treatment
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Multispecies miRNA-3 Array (mirna3), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Surgery-Induced Weight Loss Is Associated With the Downregulation of Genes Targeted by MicroRNAs in Adipose Tissue.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Treatment of severely refractory Crohns disease (CD) patients remains a clinical challenge. Recent studies show efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however the mechanisms are incompletely understood. We followed a group of patients (n=18) receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy we compared the immunological changes induced by HSCT in responders and non-responders.
Publication Title
Differences in peripheral and tissue immune cell populations following hematopoietic stem cell transplantation in Crohn's disease patients.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Time
View Samples