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GSE14230
Homo sapiens
15 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
To determine a gene/molecular fingerprint of multiple myeloma (MM) endothelial cells (MMECs), also identifying some of the vascular mechanisms that govern the malignant progression from quiescent monoclonal gammopathy of undetermined significance (MGUS). A comparative gene expression profiling (GEP) was carried out on patient-derived MMECs and MGUS endothelial cells (MGECs) using the Affymetrix U133A Arrays. Expression of selective vascular markers were also validated by RT-PCR and immunoblotting analysis in primary cultures of ECs isolated from total bone marrow (BM)-mononuclear cells. Twenty-two genes were found differently expressed in MMECs compared to MGECs (with 14 down-regulated and 8 up-regulated), thus proving that molecular differences were maintained in vitro. Specific pathways analysis revealed transcriptional and protein expression changes for key regulators of extracellular matrix formation and bone remodeling, cell-adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Specifically, we focused on six of these genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3 and SEPW1), which were not previously functionally correlated to the overangiogenic phenotype of MMECs and disease activity. These data identified distinct EC gene expression profiles and some vascular phenotypes that could influence the remodeling of the BM-microenvironment in patients with active MM. A better understanding of the linkage between genetic and epigenetic events in MM tumor/ECs may contribute to the molecular classification of the disease, thereby identifying selective targets of more effective anti-vessel/stroma therapeutic strategies.
Publication Title
Gene expression profiling of bone marrow endothelial cells in patients with multiple myeloma.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 106 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A subanalysis of the GIMEMA-MMY-3006 trial was performed to characterize treatment-emergent peripheral neuropathy (PN) in patients randomized to thalidomide-dexamethasone (TD) or bortezomib-TD (VTD) before and after double autologous transplantation (ASCT) for multiple myeloma (MM). 236 patients randomized to VTD and 238 to TD were stratified according to the emergence of grade 2 PN. Gene expression profiles (GEP) of CD138+ plasma cells were analyzed from 122 VTD-treated patients. The incidence of grade 2 PN was 35% in the VTD arm and 10% in the TD arm (p<0.001). PN resolved in 88% and 95% of patients in VTD and TD groups, respectively. Rates of complete/near complete response, progression-free and overall survival were not adversely affected by emergence of grade 2 PN. Baseline characteristics were not risk factors for PN, while GEP analysis revealed the deregulated expression of genes implicated in cytoskeleton rearrangement, neurogenesis and axonal guidance. In conclusion, in comparison with TD, incorporation of VTD into ASCT was associated with a higher incidence of PN which, however, was reversible in most of the patients and did not adversely affect their outcomes nor their ability to subsequently receive ASCT. GEP analysis suggests an interaction between myeloma genetic profiles and development of VTD-induced PN.
Publication Title
Bortezomib- and thalidomide-induced peripheral neuropathy in multiple myeloma: clinical and molecular analyses of a phase 3 study.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Plasma cell leukemia (PCL) is a rare form of plasma cell dyscrasia that presents either as a progression of previously diagnosed multiple myeloma (MM), namely secondary PCL (sPCL), or as the initial manifestation of disease, namely primary PCL (pPCL). Although presenting signs and symptoms include those seen in MM, pPCL is characterized by several aspects that clearly define more aggressive course. To provide insights into the biology of pPCL, we have investigated the transcriptional profiles of a cohort of 21 newly-diagnosed, homogeneously treated pPCL patients included in a multicenter prospective clinical trial. All but one pPCL had one of the main IGH translocations, whose associated transcriptional signatures resembled those observed in MM. A 503-gene signature was identified that distinguished pPCL from MM, from which emerged 28 genes whose trend in expression levels was found associated with the progressive stages of plasma cell dyscrasia in a large dataset of cases from multiple institutions, including samples from normal donors throughout PCL. The transcriptional pattern of the pPCL series was then evaluated in association with outcome. Three genes were identified having expression levels correlated with response to the first-line treatment with lenalidomide/dexamethasone, whereas a 27-gene signature was identified associated with overall survival independently of molecular alterations, hematological parameters and renal function. Overall, our data contribute to a fine dissection of pPCL and may provide novel insights into the molecular definition of a subgroup of high-risk pPCL.
Publication Title
Transcriptional characterization of a prospective series of primary plasma cell leukemia revealed signatures associated with tumor progression and poorer outcome.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Che-1 is a RNA Polymerase II binding protein involved in the regulation of gene transcription. Che-1 emerges as an important adaptor that connects transcriptional regulation, cell-cycle progression, checkpoint control, and apoptosis.
Publication Title
Che-1-induced inhibition of mTOR pathway enables stress-induced autophagy.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 53 Downloadable Samples
IlluminaHiSeq2000
Description
Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS cases (8,224 AS, 1,437 APA), including changes in ALS-associated genes (e.g. ATXN2 and FUS), and cases of sporadic ALS (sALS; 2,229 AS, 716 APA). Furthermore, hnRNPH and other RNA-binding proteins are predicted as potential regulators of cassette exon AS events for both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS. Overall design: Examination transcriptiome profiles in c9orf72-associated ALS, sporadic ALS and healthy control
Publication Title
Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 11 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
Primary plasma cell leukaemia (pPCL) is a rare, yet aggressive form of de novo plasma cell tumor, distinguished from secondary PCL (sPCL) which represents a leukemic transformation of pre-existing multiple myeloma (MM). Here, we performed a comprehensive molecular analysis of a prospective series of pPCLs by means of FISH, single nucleotide polymorphism (SNP) array and gene expression profiling (GEP). IGH@ translocations were identified in 87% of pPCL cases, with prevalence of t(11;14) (40%) and t(14;16) (30.5%), whereas the most frequently altered regions were located at 1p (38%), 1q (48%), 6q (29%), 8p (42%), 13q (74%), 14q (71%), 16q (53%) and 17p (35%). A relevant finding of our study was the identification of a minimal biallelical deletion (1.5 Mb) in 8p21.2 encompassing the putative tumor suppressor gene PPP2R2A that was significantly down-regulated in deleted cases. Mutations of TP53 were identified in 4 cases all but one associated with a monoallelic deletion of the gene, whereas activating mutations of BRAF occurred in one case and were absent for N- and K-RAS. To evaluate the influence of allelic imbalances in transcriptional expression we performed an integrated genomic analysis with GEP data, showing a significant dosage effect of genes involved in transcription, translation, methyltransferases activity, apoptosis as well as Wnt and NF-kB signaling pathways. Overall, we provide a compendium of genomic alterations in a prospective series of pPCLs which may contribute to our understanding of this particular form of plasma cell dyscrasia and to better elucidate the mechanisms of tumor progression in MM.
Publication Title
Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 16 Downloadable Samples
- IlluminaHiSeq2000
Description
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition characterized by loss of motor neurons in the brain and spinal cord. Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9ORF72 gene are the most common cause of the familial form of ALS (C9-ALS), as well as frontotemporal lobar degeneration and other neurological diseases. How the repeat expansion causes disease remains unclear, with both loss of function (haploinsufficiency) and gain of function (either toxic RNA or protein products) proposed. We report a cellular model of C9-ALS with motor neurons differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients carrying the C9ORF72 repeat expansion. No significant loss of C9ORF72 expression was observed, and knockdown of the transcript was not toxic to cultured human motor neurons. Transcription of the repeat was increased, leading to accumulation of GGGGCC repeat–containing RNA foci selectively in C9-ALS iPSC-derived motor neurons. Repeat-containing RNA foci colocalized with hnRNPA1 and Pur-a, suggesting that they may be able to alter RNA metabolism. C9-ALS motor neurons showed altered expression of genes involved in membrane excitability including DPP6, and demonstrated a diminished capacity to fire continuous spikes upon depolarization compared to control motor neurons. Antisense oligonucleotides targeting the C9ORF72 transcript suppressed RNA foci formation and reversed gene expression alterations in C9-ALS motor neurons. These data show that patient-derived motor neurons can be used to delineate pathogenic events in ALS. Overall design: Transcriptome profiling from iPSC derived motor neurons compared to controls
Publication Title
Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dietary methanol regulates human gene activity.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This study aimed to quantify the regulation of transcripts in the hairy skin of the back of adult rats in the condition of loss of sensory and autonomic (sympathetic) innervation (i.e., denervated). Denervated skin has reduced wound healing capacity, reduced proliferation of epidermal progenitor cells, and also expresses factors that regulate ingrowth of sensory and sympathetic axons from neighboring regions of innervated skin. It was expected that this quantification f transcript regulation would offer insight into the general and specific mechanisms that may contribute to these important biological processes.
Publication Title
categoryCompare, an analytical tool based on feature annotations.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples