Samples were taken from colorectal cancers in surgically resected specimens in 290 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. The training set of our prognosis classifier included the stage A and D samples. Validation used our stage B and C samples.
Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer.
No sample metadata fields
View SamplesThe analysis of several mammalian genomes has revealed between 20,000 to 30,000 genes in each genome, a number that may seem hard to reconcile with the large number of cell types and complex functions of these organisms. The solution to this paradox partly lies in the large array of transcripts that each gene can potentially generate through usage of alternative promoters and the variable levels of transcripts that each gene produces in different tissues and cell types. Thus, in order to understand the mechanisms that control diverse patterns of gene expression in mammals, it is necessary to accurately define the active promoters and monitor their cell or tissue-dependent activity. Previous high throughput strategies for assaying tissue-specific gene expression have primarily relied on measurements of steady-state transcript levels by microarrays or tag sequencing. Here, we employ a new experimental strategy to identify and characterize tissue specific promoters by integrating genome-wide maps of RNA polymerase II (Pol II) binding, chromatin modifications and gene expression profiles. We applied this strategy to mouse embryonic stem cells (mES), and adult brain, heart, kidney, and liver. Our results delineated 24,363 Pol II binding sites throughout the genome, 91% of which correspond to 5 end annotation based on known transcripts and cap-analysis of gene expression (CAGE) and can be regarded as promoters. A majority of these experimentally defined promoters are active in all tissues, while only 4,396 can be characterized as tissue-specific using a quantitative measure of Pol II occupancy. In general, Pol II occupancy at these tissue specific promoters is correlated with the presence of active histone modification marks. However, a set of mES- specific promoters display persistent levels of H3K4me3 in non-ES tissues despite undetectable Pol II binding and transcript. Broadly, our results expand the knowledge of tissue-specific mammalian genes and provide a resource for understanding the transcriptional programs in mammalian development and differentiation.
Genome-wide mapping and analysis of active promoters in mouse embryonic stem cells and adult organs.
No sample metadata fields
View SamplesSamples were taken from colorectal cancers in surgically resected specimens from 74 patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. Our MSI/MSS classifer was applied to these samples.
DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers.
No sample metadata fields
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Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters the immune landscape of thyroid cancer.
Specimen part, Treatment
View SamplesThe ER-membrane protein complex (EMC) functions as a transmembrane domain insertase with a broad client range, among which are proteins critical for maintaining cholesterol homeostasis. RNAseq was performed to determine whether the EMC-deficient cell lines elicited a transcriptional response to restore cholesterol homeostasis through the SREBP2 transcription factor. These data provide insight into the transcriptional programs that are activated when the insertase activity provided by the EMC is absent, from which key client proteins may be determined.
No associated publication
Sex, Specimen part, Cell line
View SamplesPAX8-PPARG fusion protein (PPFP) results from a t(2;3)(q13;p25) chromosomal translocation, is found in 30% of follicular thyroid carcinomas, and demonstrates oncogenic capacity in transgenic mice. A PPARG ligand, pioglitazone, is highly therapeutic in mice with PPFP thyroid carcinoma. We used our previously characterized transgenic mouse model of PPFP thyroid carcinoma to identify PPFP binding sites in vivo using ChIP-seq, and to identify genes and pathways regulated by PPFP with and without pioglitazone treatment via integration with RNA-seq and Affymetrix microarray data. This submission contains the Affymetrix microarray data. PPFP and pioglitazone regulated genes involved in lipid and fatty acid metabolism, ribosome function, immune processes, cell death and other cancer-related processes. The RNA-seq data yielded similar findings.
Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters the immune landscape of thyroid cancer.
Specimen part, Treatment
View SamplesMelanomas are often infiltrated by activated inflammatory cells. Thus, melanoma cells are very likely stimulated by inflammatory cytokines.
Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell isolation induces fate changes of bone marrow mesenchymal cells leading to loss or alternatively to acquisition of new differentiation potentials.
Specimen part
View SamplesMesenchymal stromal cells (MSCs) are used extensively in clinical trials; however, the potential for malignant transformation of MSCs has been raised. We examined the genomic stability versus the tumor forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immune-compromised animals. Unexpectedly, higher ploidy correlated with reduced tumor forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long non-coding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long non-coding RNA.
Polyploidization of murine mesenchymal cells is associated with suppression of the long noncoding RNA H19 and reduced tumorigenicity.
Specimen part
View SamplesMesenchymal populations include a fraction of cells exhibiting multipotency as well as others with limited differentiation range. It has been assumed that the mesenchymal cellular cascade is topped by a multipotent cell, which gives rise to progeny with diminishing differentiation potentials. Here we show that cultured mesenchymal cells, a priori exhibiting a limited differentiation potential, may gain new capacities and become multipotent following single cell isolation. These fate changes were accompanied by up-regulation of differentiation promoting genes, many of which also became H4K20me1 methylated. Early events in the process included TGF and Wnt modulation, and down-regulation of hypoxia signaling. Indeed, hypoxic conditions inhibited the observed cell changes. Overall, cell isolation from neighboring partners caused major molecular changes and particularly, a newly established epigenetic state. It is suggested that MSCs behave non-deterministically and non-hierarchically and should therefore be defined primarily by their capacity to undergo fate changes triggered by environmental cues.
Cell isolation induces fate changes of bone marrow mesenchymal cells leading to loss or alternatively to acquisition of new differentiation potentials.
Specimen part
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