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GSE98062
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Plasticity between adhesive and less-adhesive states is important for mammalian cell behaviour. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of MDA-MB-468 breast carcinoma cells which grows in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices.
Publication Title
A dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
Illumina HiSeq 2500
Description
Recurrent mutations in RNA splicing factors SF3B1, U2AF1, and SRSF2 have been reported in hematologic cancers including myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). However, SF3B1 is the only splicing associated gene to be found mutated in CLL and has been shown to induce aberrant splicing. To investigate if any other genomic aberration caused similar transcriptome changes, we clustered RNASeq samples based on an alternative 3' splice site (ss) pattern previously identified in SF3B1-mutant CLL patients. Out of 215 samples, we identified 37 (17%) with alternative 3' ss usage, the majority of which harbored known SF3B1 hotspot mutations. Interestingly, 3 patient samples carried previously unreported in-frame deletions in SF3B1 around K700, the most frequent mutation hotspot. To study the functional effects of these deletions, we used various minigenes demonstrating that recognition of canonical 3' ss and alternative branchsite are required for aberrant splicing, as observed for SF3B1 p.K700E. The common mechanism of action of these deletions and substitutions result in similar sensitivity of primary cells towards splicing inhibitor E7107. Altogether, these data demonstrate that novel SF3B1 in-frame deletion events identified in CLL result in aberrant splicing, a common biomarker in spliceosome-mutant cancers. Overall design: 13 CLL samples, 5 SF3B1 WT, 5 SF3B1 p.K700E, and 3 with in-frame deletions around the K700 position of SF3B1
Publication Title
Novel <i>SF3B1</i> in-frame deletions result in aberrant RNA splicing in CLL patients.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
- Illumina HiSeq 2000
Description
IGHV mutation status is a well-established prognostic factor in chronic lymphocytic leukemia, and also provides crucial insights into tumor cell biology and function. Currently, determination of IGHV transcript sequence, from which mutation status is calculated, requires a specialized laboratory procedure. RNA sequencing is a method that provides high resolution, high dynamic range transcriptome data that can be used for differential expression, isoform discovery, and variant determination. In this paper, we demonstrate that unselected next-generation RNA sequencing can accurately determine the IGH@ sequence, including the complete sequence of the complementarity-determining region 3 (CDR3), and mutation status of CLL cells, potentially replacing the current method which is a specialized, single-purpose Sanger-sequencing based test. Overall design: CLL cells were sequenced by mRNA-seq on the Illumina platform then subjected to the costom bioinformatic pipeline Ig-ID which yields IGH data
Publication Title
Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 83 Downloadable Samples
- IlluminaHiSeq2500
Description
Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis and cell-cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged =60 years) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. Overall design: In this study, we analyzed a large set of older CN-AML patients using custom lncRNA microarrays to investigate whether lncRNA expression is associated with clinical features, molecular abnormalities and outcome and to build a prognostic lncRNA signature that was subsequently validated using RNA sequencing. This submission represents RNA-Seq component of study.
Publication Title
Expression and prognostic impact of lncRNAs in acute myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study characterizes the response of primary human endothelial cells (human umbilical vein endothelial cells, HUVECs) to the relative shear stress changes that occur during the initiation of arteriogenesis at the entrance regions to a collateral artery network. HUVECs were preconditioned to a baseline level of unidirectional shear of 15 dynes/cm2 for 24 hours. After 24 hours preconditioning, HUVECs were subjected to an arteriogenic stimulus that mimics the shear stress changes observed in the opposing entrance regions into a collateral artery network. The arteriogenic stimulus consisted of a 100% step wise increase in shear stress magnitude to a unidirectional 30 dynes/cm2 in either the same or opposite direction of the preconditioned shear stress. This simulates either the feeding entrance to the collateral artery circuit or the region that drains into the vasculature downstream of an obstruction in a major artery, respectively. In vivo analysis of collateral growth in the mouse hindlimb showed enhanced outward remodeling in the re-entrant (direction reversing) region that reconnects to the downstream arterial tree, suggesting reversal of shear stress direction as a key enhancer of arteriogenesis. Transcriptional profiling using microarray techniques identified that the reversal of shear stress direction, but not an increase in shear stress alone, yielded a broad-based enhancement of the mechanotransduction pathways necessary for the induction of arteriogenesis.
Publication Title
Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Reversed Flow Direction.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
RhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge.
Publication Title
RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is over-expressed in CLL and is enriched proximal to genes up-regulated or de novo expressed in CLL with known function in disease pathogenesis and progression. These genes, including key members of the BCR signaling pathway, provide rationale for this therapeutic approach to identify new targets in alternative types of cancer. Additionally, we describe PLX51107, a structurally distinct BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in pre-clinical models of CLL. Herein, the discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.
Publication Title
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- IlluminaHiSeq2500
Description
We evaluated changes in mRNA stability and transcription using 4sU metabolic pulse labeling across a four hour time course following activation of Jurkat T cells with PMA and PHA Overall design: Measurement of total mRNA (T) and 4sU labeled mRNA (IP) in three biological replicates at five time points: prior to activation (U) and the first four hours after activation (1-4)
Publication Title
Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Schizosaccharomyces pombe
- 8 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Tristetraprolin is a vertebrate CCCH tandem zinc finger protein that can bind to and destabilize certain mRNAs containing AU-rich element binding sites. zfs1 is the single gene in the fission yeast, Schizosaccharomyces pombe, that encodes a protein containing the critical features of the tristetraprolin zinc finger domain. zfs1 has been linked to pheromone signal transduction control and to the coordination of mitosis, but no biological function has been ascribed to the zfs1 protein. Through a functional genomics approach we compared transcript levels in wild-type and zfs1-deficient S. pombe strains; those elevated in the zfs1-deficient strain were examined for the presence of potential tristetraprolin-like binding sites. One such potential target transcript was encoded by arz1, a gene encoding a protein of unknown function that contains armadillo repeats. arz1 mRNA decay was inhibited in the zfs1-deficient strain when it was expressed under the control of a thiamine-repressible promoter. Mutations within one AU-rich element present in the arz1 3-untranslated region protected this transcript from zfs1-promoted decay, whereas mutating another potential binding site had no effect. Binding assays confirmed a direct interaction between zfs1 and arz1 mRNA-based probes; this interaction was eliminated when key residues were mutated in either zfs1 zinc finger. zfs1 and its targets in S. pombe represent a useful model system for studies of zinc finger protein/AU-rich element interactions that result in mRNA decay.
Publication Title
Characterization of zfs1 as an mRNA-binding and -destabilizing protein in Schizosaccharomyces pombe.
Sample Metadata Fields
No sample metadata fields
View Samples