Using array comparative genomic hybridization (aCGH), a large number of deleted genomic regions have been identified in human cancers. However, subsequent efforts to identify target genes selected for inactivation in these regions have often been challenging. We integrated here genome-wide copy number data with gene expression data and non-sense mediated mRNA decay rates in breast cancer cell lines to prioritize gene candidates that are likely to be tumour suppressor genes inactivated by bi-allelic genetic events. The candidates were sequenced to identify potential mutations. This integrated genomic approach led to the identification of RIC8A at 11p15 as a putative candidate target gene for the genomic deletion in the ZR-75-1 breast cancer cell line. We identified a truncating mutation in this cell line, leading to loss of expression and rapid decay of the transcript. We screened 127 breast cancers for RIC8A mutations, but did not find any pathogenic mutations. No promoter hypermethylation in these tumours was detected either. However, analysis of gene expression data from breast tumours identified a small group of aggressive tumours that displayed low levels of RIC8A transcripts. Real-time PCR analysis of 38 breast tumours showed a strong association between low RIC8A expression and the presence of TP53 mutations (P=0.006). We demonstrate a data integration strategy leading to the identification of RIC8A as a gene undergoing a classical double-hit genetic inactivation in a breast cancer cell line, as well as in vivo evidence of loss of RIC8A expression in a subgroup of aggressive TP53 mutant breast cancers.
Data integration from two microarray platforms identifies bi-allelic genetic inactivation of RIC8A in a breast cancer cell line.
Sex, Disease, Cell line, Treatment, Time
View SamplesA study evaluating the effect of stress resistance selection of Drosophila melanogaster.
Gene expression profile analysis of Drosophila melanogaster selected for resistance to environmental stressors.
No sample metadata fields
View SamplesWe used microarrays to investigate the transcriptome of 6 days old male flies exposed to either 15 or 25 C development at either constant or fluctuating temperatures. Further, we investigated gene expression at benign (20C) and high (35C) temperatures
Thermal fluctuations affect the transcriptome through mechanisms independent of average temperature.
Sex
View SamplesMastitis in dairy cows is one of the most costly and prevalent diseases affecting dairy cows world wide. Insight in the molecular regulation of the host immune response to an E. coli infection, could help to develop new strategies to prevent cattle from E. coli infection. Here we performed a gene-expression analysis from udder tissue exposed to a controlled E. coli infection at T=24h post infection (p.i.) representing the acute phase response and at T=192h p.i. representing a chronic stage.
In depth analysis of genes and pathways of the mammary gland involved in the pathogenesis of bovine Escherichia coli-mastitis.
Specimen part, Treatment
View SamplesLiver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli). To gain an insight into the genes and pathways involved in hepatic APR of dairy cows we performed a global gene expression analysis of liver tissue sampled at different time points before and after intra-mammary (IM) exposure to E. coli lipopolysaccharide (LPS) treatment.
Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide.
No sample metadata fields
View Samplesgene expression was measured in control and heat resistance selected adult female flies before and at 8 time points after heat stress for 1h @ 36 degrees
Full genome gene expression analysis of the heat stress response in Drosophila melanogaster.
No sample metadata fields
View SamplesBackground: Genes upregulated by low oxygen have been suggested as endogenous markers for tumor hypoxia. Yet, most of the genes investigated have shown inconsistent results, which have led to concerns about their ability to be true hypoxia markers. Previous studies have demonstrated that expression of hypoxia induced genes can be affected by extracellular pH (pH e ). Methods: Five different human cell lines (SiHa, FaDu DD, UTSCC5, UTSCC14 and UTSCC15) were exposed to different oxygen concentrations and pH (7.5 or 6.3), and gene expression analyzed with microarray (Affymetrix - Human Genome U133 Plus 2.0 Array). Results: An analysis of two of the cell lines using SAM identified 461 probesets that were able to separate the four groups Normal oxygen, normal pH , Low oxygen, normal pH , Normal oxygen, low pH and Low oxygen, low pH . From here it was possible to identify a fraction of probesets induced at low oxygen independent of pH in these two cell lines, this fraction included HIG2, NDRG1, PAI1 and RORA. Further verifi cation by qPCR highlighted the necessity of using more cell lines to obtain a robust gene expression profi les. To specifi cally select pH independent hypoxia regulated genes across more cell lines, data for FaDu DD, UTSCC5, UTSCC14 and UTSCC15 were analyzed to identify genes that were induced by hypoxia in each cell line, where the induction was not affected by low pH, and where the gene was not signifi cantly induced by low pH alone. Each cell line had 65 122 probesets meeting these criteria. For genes to be considered as target genes (hypoxia inducible pH independent), genes had to be present in three of four cell lines. Conclusion: The result is a robust hypoxia profile unaffected by pH across cell lines consisting of 27 genes. This study demonstrates a way to identify hypoxia markers by microarray, where other factors in the tumor microenvironment are taken into account.
Identifying pH independent hypoxia induced genes in human squamous cell carcinomas in vitro.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Promoter DNA methylation patterns of differentiated cells are largely programmed at the progenitor stage.
Specimen part
View SamplesWe surveyed DNA methylation profiles of all human RefSeq promoters in relation to gene expression and differentiation in adipose tissue, bone marrow and muscle mesenchymal progenitors, as well as in bone marrow-derived hematopoietic progenitors. We unravel strongly overlapping DNA methylation profiles between adipose stem cells (ASCs), bone marrow mesenchymal stem cells (BMMSCs) and muscle progenitor cells (MPCs), while hematopoietic progenitor cells (HPCs) are more epigenetically distant from MSCs seen as a whole. Differentiation resolves a fraction of methylation patterns common to MSCs, generating epigenetic divergence.
Promoter DNA methylation patterns of differentiated cells are largely programmed at the progenitor stage.
Specimen part
View Samplesgene expression was measured in five independent heat resistance selected replicate lines and five control lines.
Full genome gene expression analysis of the heat stress response in Drosophila melanogaster.
No sample metadata fields
View Samples