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GSE14776
Homo sapiens
14 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
The molecular mechanisms underlying the development of bone metastases in breast cancer remain unclear. Disseminated tumour cells (DTCs) in the bone marrow of breast cancer patients are commonly identified, even in early stage disease, but their potential to initiate metastases is not known. The mechanism whereby DTCs become overt metastatic tumour cells (MTCs) is therefore, an area of considerable interest. This study explored the analysable yield of genetic material from human biopsy samples in order to describe differences in gene expression between DTCs and bone MTCs. Thirteen breast cancer patients with bone metastases underwent a CT-guided bone metastasis biopsy and a bone marrow biopsy. Tumour cells were enriched and gene expression profiling was conducted to identify differentially expressed genes. The analysable yield of sufficient RNA for microarray analysis was 60% from bone metastasis biopsies and 80% from bone marrow biopsies. A signature of 133 candidate genes differentially expressed between DTCs and MTCs was identified. Several genes relevant to breast cancer metastasis to bone (osteopontin, CTGF, parathyroid hormone receptor, EGFR) were significantly overexpressed in MTCs as compared to DTCs. Biopsies of bone metastases and bone marrow rarely yield enough tissue for robust molecular biology studies using clinical samples. The findings obtained however are interesting and seem to overlap with the bone metastasis gene expression signature described in murine xenograft models. Larger biopsy specimens or improved RNA extraction techniques may improve analysable yield and feasibility of these techniques.
Publication Title
Mechanisms and pathways of bone metastasis: challenges and pitfalls of performing molecular research on patient samples.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Since fibroblasts are a key component of the stroma with an established role in cancer, we investigated the contribution of fibroblasts to the signature observed in the stromal compartment. 13 clonally derived primary stromal fibroblasts were generated from metaplasia, dysplasia and EAC specimens. Expression of a panel of known fibroblast markers and concomitant absence of epithelial markers confirmed their fibroblastic origin. Gene expression profiling of these esophageal fibroblasts demonstrated that three ontologies related to an invasive phenotype (chemotaxis, cell adhesion, regulation of angiogenesis) differentiated cancer associated from BE fibroblasts. Furthermore, the ontologies and KEGG pathways relating to inflammation were all statistically upregulated in the fibroblast signature.
Publication Title
Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Mus musculus
- 594 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
We measured the genome-wide expression changes induced by 29 compounds targeting HDACs, DNMTs, histone lysine methyltransferases (HKMTs), and protein arginine methyltransferases (PRMTs) in pancreatic - and -cell lines.
Publication Title
Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 7 Downloadable Samples
Illumina HiSeq 4000
Description
We performed RNA-Seq analysis of wildtype and three EPAS1-/- 786-O single cell clones generated by CRISPR/Cas9 to identify the HIF-2a-responsive genes in this cell line. Samples from wildtype 786-O cells treated with DMSO or HIF-2a antagonist compound C2 were also included in this analysis. Overall design: In this experiment, we analyzed the transcriptomic profiles of 2 replicates of wildtype (WT) EPAS1+/+ 786-O cells, 1 replicate for each of the three independent EPAS1-/- 786-O single cell clones, 1 replicate of WT-786-O cells treated with DMSO and 1 replicate of WT-786-O cells treated with 10uM HIF-2a antagonist C2.
Publication Title
A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 346 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
A reference collection of genome-wide transcriptional expression data for bioactive small molecules.
Publication Title
The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Human neural stem and progenitor cells transformed with c-MYC, dominant-negative p53, constitutively active AKT and hTERT formed tumors in mice that recapitulated Group 3 medulloblastoma in terms of pathology and expression profile
Publication Title
DiSCoVERing Innovative Therapies for Rare Tumors: Combining Genetically Accurate Disease Models with In Silico Analysis to Identify Novel Therapeutic Targets.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Irritant contact dermatitis (ICD) pathogenesis is not completely understood and the genes participating in the epidermal response towards chemical irritants are only partly known. It is commonly accepted that different irritants have different mechanisms of action in the development of ICD. To define the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies (, 4 and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to sodium lauryl sulphate (SLS) or nonanoic acid (NON). Gene expression analysis using high-density oligonucleotide microarrays revealed essentially different pathway responses h after exposure: NON transiently induced the IL-6 pathway as well as a number of mitogen activated signalling cascades including ERK and growth factor receptor signalling, whereas SLS transiently downregulated cellular energy metabolism pathways. Differential expression of the cyclooxygenase-2 and matrix metalloproteinase 3 transcripts was confirmed immunohistochemically. After cumulative exposure, 883 genes were differentially expressed while 26 suggested common biomarkers were identified . In conclusion, we bring new insights into two hitherto less well elucidated phases of skin irritancy: the very initial as well as the late phase after single and cumulative exposure, respectively.
Publication Title
Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To obtain a separation of the epidermal and dermal compartments in order to examine compartment specific biological mechanisms in the skin we incubated 4 mm human skin punch biopsies in ammonium thiocyanate (NH4SCN). We wanted to test 1) the histological quality of the dermo-epidermal separation obtained by different incubation times 2) the amount and quality of extractable epidermal RNA, and 3) its impact on sample RNA expression profiles assessed by large-scale gene expression microarray analysis in both normal and inflamed skin. At 30 minutes incubation, the split between dermis and epidermis was not always histologically well-defined (i.e. occurred partly intra-epidermally) but varied between subjects. Consequently, curettage along the dermal surface of the biopsy was added to the procedure. This modified method resulted in an almost perfect separation of the epidermal and dermal compartments and satisfactory amounts of high-quality RNA were obtained. Hybridization to Affymetrix HG_U133A 2.0 GeneChips showed that ammonium thiocyanate incubation had a minute effect on gene expression resulting in only one significantly downregulated gene (cystatin E/M). We conclude that epidermis can be reproducibly and almost completely separated from the dermis of 4 mm skin biopsies by 30 min incubation in 3.8% ammonium thiocyanate combined with curettage of the dermal surface, producing high-quality RNA suitable for transcriptional analysis. Our refined method of dermo-epidermal separation will undoubtedly prove valuable in the many different settings, where the epidermal and dermal compartments need to be evaluated separately.
Publication Title
Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo-epidermal separation of 4 mm human skin biopsies.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Cytokine-induced beta-cell apoptosis is a key event for the death of pancreatic beta cells in the development of type-1 diabetes. We identified BRD0476 as a novel suppressor of cytokine-induced beta-cell apoptosis.
Publication Title
Kinase-Independent Small-Molecule Inhibition of JAK-STAT Signaling.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Lysozyme-GFP ER-HoxA9 cells were cultured in the presence of estradiol (active ER-HoxA9) or in the absence of estradiol (inactive ER-HoxA9). Samples were taken at 10 time points over a 120 hour time course of myeloid differentiation to examine those gene expression changes that accompany differentiation upon the release of HoxA9 differentiation arrest. Overall design: RNA Sequencing at 10 different time points done in duplicate
Publication Title
Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia.
Sample Metadata Fields
Cell line, Subject
View Samples