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GSE15471
Homo sapiens
72 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Expression analysis of 36 pancreatic ductal adenocarcinoma tumors and matching normal pancreatic tissue samples from pancreatic cancer patients of the Clinical Institute Fundeni (ICF) using Affymetrix U133 Plus 2.0 whole-genome chips.
Publication Title
Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
To analyze expression differences between Trp53 pro-and deficient as well as Atm pro- and deficient murine CLL tumors developing in the E-TCL1 mouse model, we analyzed splenocytes isolated from heavily infiltrated spleens of sick mice.
Publication Title
Two mouse models reveal an actionable PARP1 dependence in aggressive chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression analysis was performed from microdissected small and big HRS cells, which were taken from smears of the Hodgkin cell lines
Publication Title
Small and big Hodgkin-Reed-Sternberg cells of Hodgkin lymphoma cell lines L-428 and L-1236 lack consistent differences in gene expression profiles and are capable to reconstitute each other.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts (CAF). However, to date a deep molecular characterization of these fibroblasts is lacking. Aim of the present study therefore was a comprehensive characterization of these fibroblasts.
Publication Title
Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. To address its incomplete molecular concept, we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identified novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor / cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM towards a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.
Publication Title
Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The activation of the transcription factor NF-E2-related factor 2 (Nrf2) maintains cellular homeostasis in response to oxidative stress by the regulation of multiple cytoprotective genes. Without stressors the activity of Nrf2 is inhibited by its interaction with the kelch-like ECH-associated protein 1 (Keap1). Here, we describe RA839, a small molecule that binds non-covalently to the Nrf2-interacting kelch domain of Keap1 with a Kd of approximately 6 M, as demonstrated by X-ray co-crystallization and isothermal titration calorimetry. Whole-genome DNA arrays showed that at 10 M RA839 significantly regulated 105 genes in bone marrow-derived macrophages. Canonical pathway mapping of these genes revealed an activation of pathways linked with Nrf2 signalling. These pathways were also activated after the activation of Nrf2 by the silencing of Keap1 expression. RA839 regulated only two genes in Nrf2 knockout macrophages. Similar to the activation of Nrf2 by either silencing of Keap1 expression or by the reactive compound CDDO-Me, RA839 prevented the induction of both inducible nitric oxide synthase expression and nitric oxide release in response to lipopolysaccharides in macrophages. In mice RA839 acutely induced Nrf2-target gene expression in liver. RA839 is a selective inhibitor of the Keap1/Nrf2 interaction and a useful tool compound to study the biology of Nrf2.
Publication Title
Characterization of RA839, a Noncovalent Small Molecule Binder to Keap1 and Selective Activator of Nrf2 Signaling.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 19 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2-neu) of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs) within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC) and six Her2+. We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER+ cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs may contribute to the more invasive properties and unfavorable prognosis of Her2+ breast cancer. These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer.
Publication Title
Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The molecular biology of metastatic potential in melanoma has been studied many times previously and changes in the expression of many genes have been linked to metastatic behaviour. What is lacking is a systematic characterization of the regulatory relationships between genes whose expression is related to metastatic potential. Such a characterization would produce a molecular taxonomy for melanoma which could feasibly be used to identify epigenetic mechanisms behind changes in metastatic behaviour. To achieve this we carried out three separate DNA microarray analyses on a total of 86 cultures of melanoma. Significantly, multiple testing correlation revealed that previous reports describing correlations of gene expression with activating mutations in BRAF or NRAS were incorrect and that no gene expression patterns correlate with the mutation status of these MAPK pathway components. Instead, we identified three different sample cohorts (A, B and C) and found that these cohorts represent melanoma groups of differing metastatic potential. Cohorts A and B were susceptible to TGFbeta-mediated inhibition of proliferation and had low motility. Cohort C was resistant to TGFb and demonstrated high motility. Meta-analysis of the data against previous studies linking gene expression and phenotype confirmed that cohorts A and C represent transcription signatures of weakly and strongly metastatic melanomas, respectively. Gene expression co-regulation suggested that signalling via TGFbeta-type and Wnt pathways underwent considerable change between cohorts. These results suggest a model for the transition from weakly to strongly metastatic melanomas in which TGFbeta-type signalling upregulates genes expressing vasculogenic/extracellular matrix remodeling factors and Wnt signal inhibitors, coinciding with a downregulation of genes downstream of Wnt signalling.
Publication Title
Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The molecular biology of metastatic potential in melanoma has been studied many times previously and changes in the expression of many genes have been linked to metastatic behaviour. What is lacking is a systematic characterization of the regulatory relationships between genes whose expression is related to metastatic potential. Such a characterization would produce a molecular taxonomy for melanoma which could feasibly be used to identify epigenetic mechanisms behind changes in metastatic behaviour. To achieve this we carried out three separate DNA microarray analyses on a total of 86 cultures of melanoma. Significantly, multiple testing correlation revealed that previous reports describing correlations of gene expression with activating mutations in BRAF or NRAS were incorrect and that no gene expression patterns correlate with the mutation status of these MAPK pathway components. Instead, we identified three different sample cohorts (A, B and C) and found that these cohorts represent melanoma groups of differing metastatic potential. Cohorts A and B were susceptible to TGFbeta-mediated inhibition of proliferation and had low motility. Cohort C was resistant to TGFb and demonstrated high motility. Meta-analysis of the data against previous studies linking gene expression and phenotype confirmed that cohorts A and C represent transcription signatures of weakly and strongly metastatic melanomas, respectively. Gene expression co-regulation suggested that signalling via TGFbeta-type and Wnt pathways underwent considerable change between cohorts. These results suggest a model for the transition from weakly to strongly metastatic melanomas in which TGFbeta-type signalling upregulates genes expressing vasculogenic/extracellular matrix remodeling factors and Wnt signal inhibitors, coinciding with a downregulation of genes downstream of Wnt signalling.
Publication Title
Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Some infectious agents are associated with non-Hodgkin lymphoma development. Here we have used p53-deficient mice chronically injected with Streptococcus pneumoniae (Spn) with the aim to develop an animal model of infection-associated lymphomagenesis. We show that repeated stimulations with heat-killed Spn significantly enhanced the incidence of peripheral T-cell lymphoma (PTCL) in these mice. Phenotypic studies and gene expression profile analyses indicate that these PTCL arose from chronically stimulated natural killer T (NKT) cells, a T cell lineage that exhibits unique properties. Furthermore, lymphoma development was blocked when these PTCL were transferred to recipients lacking CD1d expression or treated with blocking CD1d mAbs, thus demonstrating that in vivo TCR/CD1d interactions are required for these PTCL survival. In conclusion, we have identified a new entity of peripheral T-cell lymphoma that originates from CD1d-restricted natural killer T (NKT) cells. Our results could refine the classification of PTCL and pave the way for the development of new immunotherapeutic approaches.
Publication Title
CD1d-restricted peripheral T cell lymphoma in mice and humans.
Sample Metadata Fields
Age, Specimen part
View Samples