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GSE60789
Homo sapiens
55 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SCANB SubSeries listed below.
Publication Title
The Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 55 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Breast cancer exhibits significant molecular, pathological, and clinical heterogeneity. Current clinicopathological evaluation is imperfect for predicting outcome, which results in overtreatment for many patients, and for others, leads to death from recurrent disease. Therefore, additional criteria are needed to better personalize care and maximize treatment effectiveness and survival. To address these challenges, the Sweden Cancerome Analysis Network - Breast (SCAN-B) consortium was initiated in 2010 as a multicenter prospective study with longsighted aims to 1) analyze breast cancers with next-generation genomic technologies for translational research in a population-based manner and integrated with healthcare; 2) decipher fundamental tumor biology from these analyses; 3) utilize genomic data to develop and validate new clinically-actionable biomarker assays; and 4) build the infrastructure for real-time clinical implementation of molecular diagnostic, prognostic, and predictive tests. In the first phase, we focus on molecular profiling by next-generation RNA-sequencing on the Illumina platform. In the three years from August 30, 2010 through August 31, 2013, we have consented and enrolled 3,979 patients with primary breast cancer at the seven hospital sites in South Sweden, representing approximately 85% of eligible patients in the catchment area. Pre-operative blood samples have been collected for 3,942 (99%) patients and primary tumor specimens collected for 2,929 (74%) patients. Herein we describe the study infrastructure and present initial proof of concept results from prospective RNA-sequencing including tumor molecular subtyping and detection of driver gene mutations. We demonstrate that large-scale population-based collection and RNA-sequencing analysis of breast cancer is feasible. The SCAN-B Initiative should significantly reduce the time to discovery, validation, and clinical implementation of novel molecular diagnostic and predictive tests. We welcome the participation of additional comprehensive cancer treatment centers.
Publication Title
The Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Imatinib has become the current standard therapy for patients with chronic myelogenous leukaemia (CML). For a better understanding of the Imatinib-related molecular effects in vivo, we assessed gene expression profiles of Philadelphia Chromosome positive (Ph+) CD34+ cells from peripheral blood of 6 patients with de novo CML in chronic phase. After 7 days of treatment with Imatinib the Ph+ CD34+ cells were reassessed to look for changes in the transcriptome. The expression level of 303 genes was significantly different comparing the transcriptome of the Ph+ CD34+ cells before and after 7 days of Imatinib therapy (183 down-regulated, 120 up-regulated, lower bound 1.2-fold). For a substantial number of genes governing cell cycle and DNA replication, the level of expression significantly decreased (CDC2, RRM2, PCNA, MCM4). On the other hand, therapy with Imatinib was associated with an increase of genes related to adhesive interactions, such as L-selectin or CD44. A group of 8 genes with differential expression levels were confirmed using a gene specific quantitative real-time PCR. Thus, during the first week of treatment, Imatinib is preferentially counteracting the bcr-abl induced effects related to a disturbed cell cycle and defective adhesion of leukemic Ph+ CD34+ cells.
Publication Title
Early in vivo changes of the transcriptome in Philadelphia chromosome-positive CD34+ cells from patients with chronic myelogenous leukaemia following imatinib therapy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We found that composition of cell subsets within the CD34+ cell population is markedly altered in chronic phase (CP) chronic myeloid leukemia (CML). Specifically, proportions and absolute cell counts of common myeloid progenitors (CMP) and megakaryocyte-erythrocyte progenitors (MEP) are significantly greater in comparison to normal bone marrow whereas absolute numbers of hematopoietic stem cells (HSC) are equal. To understand the basis for this, we performed gene expression profiling (Affymetrix HU-133A 2.0) of the distinct CD34+ cell subsets from six patients with CP CML and five healthy donors. Euclidean distance analysis revealed a remarkable transcriptional similarity between the CML patients' HSC and normal progenitors, especially CMP. CP CML HSC were transcriptionally more similar to their progeny than normal HSC to theirs, suggesting a more mature phenotype. Hence, the greatest differences between CP CML patients and normal donors were apparent in HSC including downregulation of genes encoding adhesion molecules, transcription factors, regulators of stem-cell fate and inhibitors of cell proliferation in CP CML. Impaired adhesive and migratory capacities were functionally corroborated by fibronectin detachment analysis and transwell assays, respectively. Based on our findings we propose a loss of quiescence of the CML HSC on detachment from the niche leading to expansion of myeloid progenitors.
Publication Title
The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Genome-wide transcriptional profiling of purified telomerase deficient (Terc-/-) and WT LSCs was performed in order to gain insights into the mechanisms underlying the susceptibilities of Terc-/- LSCs in vivo.
Publication Title
Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The root epidermis of Arabidopsis provides a simple and experimentally useful model for studying the molecular basis of cell fate and differentiation. The goal of this study was to define the transcript changes in the root epidermis of mutants associated with root epidermis cell specification, including mutants that lack a visible phenotypic alteration (try, egl3, myb23, and ttg2). Transcript levels were assessed by purifying populations of root epidermal cells using fluorescence-based cell-sorting with the WER::GFP transgene. These microarray results were used to compare the effects of single and double mutants on the gene regulatory network that controls root epidermal cell fate and differentiation in Arabidopsis.
Publication Title
Tissue-specific profiling reveals transcriptome alterations in Arabidopsis mutants lacking morphological phenotypes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
IlluminaHiSeq2000
Description
Acetyltransferases and histone deacetylases regulate gene expression at the level of chromatin, mainly by affecting transcription. In this study, we report that hyperacetylation induced by inhibition of histone deacetylases (HDACs) causes massive degradation of mRNA. The effect is promoter-independent and affects poly-A mRNA globally. HDAC inhibition leads to the removal of poly-A tails from mRNAs through activation of the deadenylase CAF1a, which we find to be acetylated together with its activator BTG2 by the histone acetyl transferases (HATs) p300 and CBP. By mutation of critical lysine residues, we provide evidence that acetylation of CAF1a and BTG2 induces enhanced poly-A mRNA degradation. Our study reveals a fundamental mechanism by which cells coordinate epigenetic and transcriptional control of gene expression with posttranscriptional control of poly-A mRNA stability. In this experiment, HeLa cells were exposed to the HDAC inhibitor trichostatin A (TSA) for 16 hours, followed by treatment with actinomycin D. Total RNA was isolated after 0, 2, 4 and 6 hours, and analysed by RNA sequencing. The half-lives of 7431 RNAs were calculated after normalization to rRNA (18S + 28S) levels. The experiment shows that TSA treatment causes a general reduction of poly-A RNA stability, while replication-dependent histone mRNA stability is not affected. Overall design: RNA half-lives were measured in TSA-treated or untreated HeLa cells by RNA-Seq using Illumina HiSeq 2000.
Publication Title
Acetylation-Dependent Control of Global Poly(A) RNA Degradation by CBP/p300 and HDAC1/2.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Flowering time is a complex trait regulated by many genes that are integrated in different genetic pathways. Different genetic screenings carried out during the past decades have revealed an intrincated genetic regulatory network governing this trait. Efforts aimed at improving our understanding of how such genetic pathways respond to genetic and enviromental cues are needed.
Publication Title
The arabidopsis DNA polymerase δ has a role in the deposition of transcriptionally active epigenetic marks, development and flowering.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Multiple myeloma (MM) is a clonal plasma cell disorder frequently accompanied by hematopoietic impairment. Genomic profiling of distinct HSPC subsets revealed a consistent deregulation of signaling cascades, including TGF beta signaling, p38MAPK signaling and pathways involved in cytoskeletal organization, migration, adhesion and cell cycle regulation in MM patients.
Publication Title
Multiple myeloma-related deregulation of bone marrow-derived CD34(+) hematopoietic stem and progenitor cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples