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GSE52904
Homo sapiens
66 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 66 Downloadable Samples
Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The contribution of copy number (CN)-altered genes in cervical carcinogenesis is unknown owing to a lack of correlation with gene expression. We mapped CN-altered genes in 31 cervical cancers (CCs), and investigated the expression of 21,000 genes in 55 CCs using microarrays. Biological processes associated with genes deregulated by gene dosage and the relationship between gene dosage and patient survival were investigated. CN-altered genome (CN-AG) percentages varied widely among tumors from 0% to 32.2% (mean = 8.1 8.9). Tumors were classified as low (mean = 0.5 0.6, n = 11), medium (mean = 5.4 2.4, n = 10), or high (mean = 19.2 6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated by gene dosage; by contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.6% of deregulated genes in whole tumors (r2 = 0.236, p = 0.006; analysis of variance), including those in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This result suggests that the remaining genes are not deregulated directly by gene dosage but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profiles of APC/C-proteasome-dependent proteolysis and glycolysis were associated with poor patient survival, although only the first 2 correlations were statistically significant (p < 0.05, log-rank test). The data suggest that inhibitors of APC/C-dependent proteasome proteolysis and glycolysis may be useful treatments in these patients.
Publication Title
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Although Human papillomavirus infection is the main causal factor for cervical cancer (CC), there is data suggesting genetic factors could modulate the risk and progression of CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to cervical cancer, HPV infection and HPV types, a case-control study was performed in the Mexican mestizo population. The polymorphism of mtDNA D-Loop was investigated in 187 cervical cancer patients and 270 healthy controls. D-loop was amplified from a blood DNA sample and analyzed by sequencing. HPV was detected and typed in cervical scrapes from both groups. mtDNA polymorphisms were compared in the whole samples and stratified by HPV types. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (OR=1.6, 95% CI: 1.05-2.58) and showed an additive effect of 36% over the risk conferred by the HPV (OR=153, 95% CI: 65.4-357.5). The frequency of HPV 16, 18, 31 and 45 in cancer samples was similar in all haplogroups but one (D1). It showed a very low frequency of HPV16, any HPV18 and high frequency of HPVs 31, 45 and other types. Two mtDNA genes (MT-TD, MTTK) could be involved in the increased risk conferred by the haplogroup B2, since they were up-regulated exclusively in B2 tumors (p<0.05, t-test). These findings will contribute to clarify the importance of genetic factors in CC.
Publication Title
The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The synthetic glucocorticoids prednisolone and dexamethasone regulate the same genes in acute lymphoblastic leukemia cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: Glucocorticoids (GCs) cause apoptosis in malignant cells of lymphoid lineage by transcriptionally regulating a plethora of genes. As a result, GCs are included in almost all treatment protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukemia (chALL). The most commonly used synthetic GCs in the clinical setting are prednisolone and dexamethasone. While the latter has a higher activity and more effectively reduces the tumor load in patients, it is also accompanied by more serious adverse effects than the former. Whether this difference might be explained by regulation of different genes by the two GCs has never been addressed.
Publication Title
The synthetic glucocorticoids prednisolone and dexamethasone regulate the same genes in acute lymphoblastic leukemia cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: Glucocorticoids (GCs) cause apoptosis in malignant cells of lymphoid lineage by transcriptionally regulating a plethora of genes. As a result, GCs are included in almost all treatment protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukemia (chALL). The most commonly used synthetic GCs in the clinical setting are prednisolone and dexamethasone. While the latter has a higher activity and more effectively reduces the tumor load in patients, it is also accompanied by more serious adverse effects than the former. Whether this difference might be explained by regulation of different genes by the two GCs has never been addressed.
Publication Title
The synthetic glucocorticoids prednisolone and dexamethasone regulate the same genes in acute lymphoblastic leukemia cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 80 Downloadable Samples
NextSeq 500
Description
We use single-cell RNA sequencing (scRNA-seq) to explore the transcriptional changes associated with estrogen-induced dysplasia in mouse ovarian surface epithelial cells Overall design: scRNA-seq of control and estrogen-treated (100nM) mOSE cultured for 15 days. scRNA-seq was performed using the Fluidigm HT 3' RNA-seq protocol on the Fluidigm C1
Publication Title
Single-cell RNA-sequencing reveals transcriptional dynamics of estrogen-induced dysplasia in the ovarian surface epithelium.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: ETV6/RUNX1 (E/R) (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL) and also most likely the crucial factor for disease initiation, whereas its role in leukemia propagation and maintenance remains largely elusive. To address this issue we performed a shRNA-mediated knock-down (KD) of the E/R fusion gene and investigated the ensuing consequences on genome-wide gene expression patterns and deducible regulatory functions in two E/R-positive leukemic cell lines. Findings: Microarray analyses identified 777 genes whose expression was substantially altered. Although approximately equal proportions were either up- (KD-UP) or down-regulated (KD-DOWN), the effects on biological processes and pathways differed considerably. The E/R KD-DOWN set was significantly enriched for genes included in the cell activation, immune response, apoptosis, signal transduction and development and differentiation categories, whereas in the E/R KD-UP set only the PI3K/AKT/mTOR signaling and hematopoietic stem cells categories became evident. Comparable expression signatures obtained from primary E/R-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories stem cell properties, B-cell differentiation, immune response, cell adhesion and DNA damage with RT-qPCR. Conclusion: The results of our analyses provide the first preliminary evidence that the continuous expression of the E/R fusion gene interferes with regular B-cell development by repressing key functions that are necessary under physiological circumstances. E/R may thus constitute also the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets.
Publication Title
The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: huex10stv2_67_020 (huex10st)
Description
Glucocorticoids (GCs) are a central component in treating childhood acute lymphoblastic leukemia (chALL). They mainly act via regulating gene transcription. However, control of mRNA translation by GC has never been assessed systematically. In our research, T- and precursor B-ALL cells were cultured with and without GC for 6 hours and subjected to translational profiling, a technique combining sucrose gradient fractionation and microarray analysis of mRNA in different fractions. Analysis of GC regulation in different pools revealed no significant differences in regulation of mRNA translation by GC, suggesting no evidence for translational regulation by GC.
Publication Title
Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
EWS-FLI1 is a chimeric ETS transcription factor that is, due to a chromosomal rearrangement, specifically expressed in Ewings sarcoma family tumors (ESFT) and is thought to be the initiating event in the development of the disease. Previous genomic profiling experiments have identified a number of EWS-FLI1 regulated genes and genes that discriminate ESFT from other sarcomas, but so far a comprehensive analysis of EWS-FLI1 dependent molecular functions characterizing this aggressive cancer is lacking. In this study a molecular function map of ESFT was constructed based on an integrative analysis of gene expression profiling experiments on a uniform microarray platform following EWS-FLI1 knockdown in a panel of five ESFT cell lines, and on gene expression data from the same platform of 59 primary ESFT tumors. Based on the assumption that EWS-FLI1 is the driving transcriptional force in ESFT pathogenesis, we predicted an inverse correlation of gene expression for EWS-FLI1 regulated genes between the putative tissue of origin and the cell lines under EWS-FLI1 knockdown conditions. Consistent with recent reports, mesenchymal progenitor cells (MPC) were found to fit this hypothesis best and were therefore used as the reference tissue for the construction of the molecular function map in ESFT.
Publication Title
A molecular function map of Ewing's sarcoma.
Sample Metadata Fields
No sample metadata fields
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