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GSE118022
Mus musculus
24 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Affymetric arrays were performed on thyroid samples collected from GEMMs: normal thyroid, TPO-Cre/LSL-Braf (PTC), TPO-Cre/tetO-BRAF/LSL-rtTAiresGFP/p53-flox (ATC) and TPO-Cre/tetO-BRAF/LSL-rtTAiresGFP/p53-flox (recurrent tumors)
Publication Title
Hgf/Met activation mediates resistance to BRAF inhibition in murine anaplastic thyroid cancers.
Sample Metadata Fields
Specimen part
View Samples- 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
- 58 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Background: The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling. Methods: The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). The 20 patients were then grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3, HSAL2, and PACE4, were selected for their potential biological significance in a larger cohort of 49 patients by quantitative real-time RT-PCR. Results: Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of GLUT3, HSAL2 and PACE4, respectively. Univariate analyses demonstrated that GLUT3 over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). HSAL2 was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.0467). In survival studies, only GLUT3 showed a prognostic value with disease-specific (P=0.049), relapse-free (P-0.0042) and overall survival (P=0.003). PACE4 mRNA expression failed to show correlation with any of the relevant parameters. Conclusions: The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.
Publication Title
Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
IonTorrentProton
Description
Phosphoinositide-3-kinase (PI3K)-a inhibitors are clinically active in squamous carcinoma (SCC) of the head and neck (H&N) bearing mutations or amplification of PIK3CA. We aimed to identify potential mechanism of resistance and have observed that SCCs cells overcome the antitumor effects of the PI3Ka inhibitor BYL719 by maintaining PI3K-independent activation of the mammalian target of rapamycin (mTOR). The persistent mTOR activation is mediated by the tyrosine kinase receptor AXL. We found that AXL is overexpressed in resistant tumors, dimerizes with the epidermal growth factor receptor (EGFR), phosphorylates EGFR tyrosine 1173, resulting in activation of phospholipase C? (PLC?)- protein kinase C (PKC) that, in turn, activates mTOR. Finally, simultaneous treatment with PI3Ka and either EGFR, AXL or PKC inhibitors reverts this resistance. Overall design: RNAseq from acquired resistant cells CAL33B, K180B were compared to their parental counterpart CAL33 and K180, respectively. K180 is a shortcut of KYSE180, and B stands for BYL719. Duplicate of parental sensitive cells and K180B, and triplicate for CAL33B.
Publication Title
AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Schizosaccharomyces pombe
- 8 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Nitric oxide being a versatile molecule inside biological systems, from being both a cell signaling molecule to a potent stress agent, has significant effect in the transcriptional response in fission yeast.
Publication Title
Global transcriptomic profiling of Schizosaccharomyces pombe in response to nitrosative stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Sound vibration (SV) causes various developmental and physiological changes in plants. It strongly suggests the existence of sophisticated molecular mechanisms for SV perception and signaling in plants. However, the underlying molecular mechanism of SV-mediated plant responses remains elusive. Herein, we investigated the transcript changes in Arabidopsis thaliana upon five different single frequencies of SV treatment.
Publication Title
Plant acoustics: in the search of a sound mechanism for sound signaling in plants.
Sample Metadata Fields
Age, Specimen part
View Samples- Danio rerio
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
identification of differentially expressed genes in gas6 homozygous mutant hindbrain when compared to wildtype hindbrain in zebrafish Overall design: Total RNA was extracted from dissected hindbrain of gas6 homzygous mutants and wildtype embryos at 48hpf using the RNeasy Mini Kit (Qiagen). Three libraries from wildtype embryos and three libraries from gas6 mutants were then generated from 3mg RNA using the TruSeq Stranded mRNA Library Prep Kit (Illumina). All libraries were analyzed for quality on a bioanalyzer prior to sequencing (Agilent 2100 BioAnalyzer).
Publication Title
Analysis of novel caudal hindbrain genes reveals different regulatory logic for gene expression in rhombomere 4 versus 5/6 in embryonic zebrafish.
Sample Metadata Fields
Specimen part, Subject
View Samples- Caenorhabditis elegans
- 36 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Discriminating pathogenic bacteria from energy-harvesting commensals is key to host immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the Caenorhabidits elegans innate immune response. Using whole genome transcriptional profiling, O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes as well as genes shared with the p38 MAPK/PMK-1 pathway. Moreover, genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies further revealed that nutrient-responsive OGT-1 acts through the conserved -catenin (BAR-1) pathway and in concert with p38 MAPK/PMK-1 to modulate the immune response to S. aureus. The participation of the nutrient sensor O-GlcNAc transferase in an immunity module conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response.
Publication Title
Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity.
Sample Metadata Fields
Treatment
View Samples- Escherichia coli
- 14 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Escherichia coli exhibits diauxic growth in sugar mixtures due to CRP-mediated catabolite repression and inducer exclusion related to phosphotransferase system enzyme activity. Replacement of the native crp gene with a catabolite repression mutant (referred to as crp*) alleviates diauxic effects in E. coli and enables co-utilization of glucose and other sugars. While previous studies have examined the effects of expressing CRP* mutants on the expression of specific catabolic genes, little is known about the global transcriptional effects of CRP* expression.
Publication Title
Transcriptional effects of CRP* expression in Escherichia coli.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sickle cell disease is characterized by hemolysis, vaso-occlusion and ischemia reperfusion injury. These events cause endothelial dysfunction and vasculopathies in multiple systems
Publication Title
Global gene expression profiling of endothelium exposed to heme reveals an organ-specific induction of cytoprotective enzymes in sickle cell disease.
Sample Metadata Fields
Specimen part, Treatment
View Samples