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GSE69029
Homo sapiens
118 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 118 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is an early and deep tumour burden reduction; this characterizes and defines the complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC derived from MM patients who achieved CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy.
Publication Title
The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
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
- 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
- 121 Downloadable Samples
NextSeq 500
Description
We used mammosphere formation assay and label-retention assay as functional cellular approaches to enrich for cells with different degree of cancer stem cell properties in the breast cancer cell line MDA-MB-231 and performed single-cell RNA sequencing Overall design: Single cells from three different populations: 30 cells from G1 cell cycle phase cultured in adherent conditions, 46 cells with low proliferation cultured in non-adherent conditions (mammosphere assasy), 45 cells with high proliferation cultured in non-adherent conditions (mammosphere assay)
Publication Title
Erratum: Identification of Breast Cancer Stem Cell Related Genes Using Functional Cellular Assays Combined With Single-Cell RNA Sequencing in MDA-MB-231 Cells.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to characterize the global changes in gene expression within the ascending aorta of mice due to conditional disruption of TGF- signaling in smooth muscle and/or due to heterozygous fibrillin-1 mutation.
Publication Title
Tgfbr2 disruption in postnatal smooth muscle impairs aortic wall homeostasis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We have used microarrays to identify individual genes and pathways regulated by Gq/11 or G12/13 signalling in type II alveolar epithelial cells isolated from the lungs of knockout mice.
Publication Title
Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33-mediated macrophage polarization and emphysema.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Neural stem/progenitor cells were isolated from the lateral ventricle wall of 4-6 week-old CD1 mice and grown as neurospheres under low density culture conditions. Test cells were transduced with bicistronic retroviral constructs for the over-expression of Bmi1 together with eGFP, and control cells were transduced with an empty vector construct expressing eGFP only. To identify genes, which are regulated by BMI1 in neural stem/progenitor cells, the gene expression profiles of neurosphere cells over-expressing Bmi1 were compared empty vector control cells using Affymetrix Gene mouse ST1.0 arrays
Publication Title
The putative tumor suppressor gene EphA7 is a novel BMI-1 target.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- NextSeq 500
Description
Recurrent chromosomal translocations involving the mixed lineage leukemia gene (MLL) give rise to highly aggressive acute leukemia associated with poor clinical outcomes. The preferential involvement of chromatin-associated factors in MLL rearrangements belies a dependency on transcriptional control. To identify new targets for therapeutic development in MLL, we performed a genome-scale CRISPR-Cas9 knockout screen in MLL-AF4 leukemia. Among validated targets, we identified the transcriptional regulator, ENL, as an unrecognized dependency particularly indispensable for proliferation. To explain the mechanistic role for ENL in leukemia pathogenesis and the dynamic role in transcription control, we pursued a chemical genetic strategy utilizing targeted protein degradation. ENL loss suppresses transcription initiation and elongation genome-wide, with pronounced effects at genes featuring disproportionate ENL load. Importantly, ENL-dependent leukemic growth was contingent upon an intact YEATS epigenomic reader domain. These findings reveal a novel dependency in acute leukemia and a first mechanistic rationale for disrupting YEATS domains in disease. Overall design: RNA-seq in MV4;11 (Cas9; ENL-FKBP(F36V); ENL -/-) cells with dTAG-13 and EPZ-5676 treatment
Publication Title
Transcription control by the ENL YEATS domain in acute leukaemia.
Sample Metadata Fields
Cell line, Subject
View Samples