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GSE54077
Homo sapiens
7 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTS) may provide important insight into the biology of GBM. We identified 7 patients with GBM treated at Memorial Sloan-Kettering Cancer Center (MSKCC) with survival greater than 48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTS in two independent cohorts (TCGA and REMBRANDT) and analyzed the transcriptomal characteristics of these LTS. The median overall survival of our cohort was 62.5 months. LTS were distributed between the proneural (n=2), neural (n=2), classical (n=2) and mesenchymal (n=1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identity. The majority of the MSKCC LTS (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutations, and IDH mutation occurred in a minority of the TCGA LTS as well. A set of 42 genes was found to be differentially expressed in the MSKCC and TCGA LTS. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression.
Publication Title
Transcriptional diversity of long-term glioblastoma survivors.
Sample Metadata Fields
Disease stage
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 58 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glioma CIMP (G-CIMP) is a powerful determinant of tumor pathogenicity but the molecular cause of G-CIMP is a fundamental question that is unresolved. Here, we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), directly causes the G-CIMP in gliomas by remodeling the methylome.
Publication Title
IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Activation or maintenance of a leukemia stem cell self-renewal pathway in downstream myeloid cells is an important component of AML development
Publication Title
The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mitochondrial defects are associated with a spectrum of human disorders, ranging from rare, inborn errors of metabolism to common, age-associated diseases such as diabetes and neurodegeneration. In lower organisms, genetic retrograde signaling programs have been identified that promote cellular and organism survival in the face of mitochondrial dysfunction. Here, we characterized the transcriptional component of the human mitochondrial retrograde response in an inducible model of mitochondrial dysfunction.
Publication Title
Mitochondrial dysfunction remodels one-carbon metabolism in human cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Uremic media calcification is not only driven by systemic factors such as hyperphosphatemia, but also crticially dependent on vascular smooth muscle cells per se. We hypothesized that the different developmental origins of vscular smooth muscle cells might lead to a heterogeneous susceptibility to develop media calcification.
Publication Title
Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 8 Downloadable Samples
NextSeq 500
Description
Selenium, one of a class of selenocysteine-containing proteins (selenoproteins), is an essential micronutrient known for its cancer prevention properties. Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LCMS/ MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of ascorbate and methionine, while increasing methionine sulfoxide. Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development. Overall, our findings establish that seph regulates redox homeostasis and suppresses DNA damage. We hypothesize that SepH deficiency may contribute to the increased cancer risk observed in cohorts with low selenium levels. Overall design: 4 WT zebrafish samples and 4 SepH mutant samples
Publication Title
Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis.
Sample Metadata Fields
Subject
View Samples- Rattus norvegicus
- 45 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver from Sprague Dawley rats dosed with myclobutanil (300 mg/kg/day) or triadimefon (175 mg/kg/day) for 6, 24 or 336 hours. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism and fatty acid metabolism were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis.
Publication Title
Toxicogenomic effects common to triazole antifungals and conserved between rats and humans.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The triazole antifungals myclobutanil (MYC), propiconazole (PPZ) and triadimefon (TDF) [Propiconazole CASNR 60207-90-1; Triadimefon CASNR 43121-43-3; Myclobutanil CASNR 88671-89-0] all disrupt steroid hormone homeostasis and cause varying degrees of hepatic toxicity. To identify biological pathways consistently activated across various study designs, gene expression profiling was conducted on livers from rats following acute, repeated dose, or prenatal to adult exposures. To explore conservation of responses across species, gene expression from these rat in vivo studies were also compared to in vitro data from rat and human primary hepatocytes exposed to MYC, PPZ, or TDF. Pathway and gene level analyses across time of exposure, dose, and species identified patterns of expression common to all three triazoles, which were also conserved between rodents and humans. Pathways affected included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Many of the differentially expressed genes are regulated by the nuclear receptors CAR, PPAR alpha and PXR, including ABC transporter genes (Abcb1 and MDR1), genes significant to xenobiotic, fatty acid, sterol and steroid metabolism (Cyp2b2 and CYP2B6; Cyp3a1 and CYP3A4; Cyp4a22 and CYP4A11) and xxx (Ugt1a1 and UGT1A1). Modulation of hepatic sterol and steroid metabolism is a plausible mechanism for triazole induced increases in serum testosterone. The gene expression changes caused by all three triazoles appear to focus on pathways regulating lipid and testosterone homeostasis, identifying potential common mechanisms of triazole hepatotoxicity that are conserved between rodents and humans.
Publication Title
Toxicogenomic effects common to triazole antifungals and conserved between rats and humans.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 35 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver and testis from Wistar Han IGS rats fed myclobutanil (M: 500, 2000 ppm), propiconazole (P: 500, 2500 ppm), or triadimefon (T: 500, 1800 ppm) from gestation day six to postnatal day 92. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Triadimefon induced a distinctive expression profile of genes involved in liver sterol biosynthesis. There were no common pathways modulated by all three triazoles in the testis. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism (Aldh1a1, Cyp1a1, Cyp2b2, Cyp3a1, Slco1a4, Udpgtr2), fatty acid metabolism (Cyp4a10, Pc, Ppap2b), and steroid metabolism (Srd5a1, Ugt1a1, Ugt2a1) were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism, sterol biosynthesis, and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis.
Publication Title
Mode of action for reproductive and hepatic toxicity inferred from a genomic study of triazole antifungals.
Sample Metadata Fields
No sample metadata fields
View Samples