Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ena-DATASET-ICR-GM-05-05-2015-22:13:47:053-131 - samples

ABSTRACT: 463 newly diagnosed patients from the UK Myeloma XI clinical trial (NCT01554852) underwent whole exome sequencing plus targeted capture of the IGH/K/L and MYC loci. 200 ng of DNA were processed using NEBNext DNA library prepartion kit and hybridised to the SureSelect Human All Exon V5 Plus. Four samples were pooled and run on one lane of a HiSeq 2000 using 76-bp paired end reads. DNA from CD138+ selected bone marrow cells (myeloma tumour) as well as peripheral white blood cells were analysed and somatic mutations detected.

PROVIDER: EGAD00001001358 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Publications

APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma.

Walker Brian A BA Wardell Christopher P CP Murison Alex A Boyle Eileen M EM Begum Dil B DB Dahir Nasrin M NM Proszek Paula Z PZ Melchor Lorenzo L Pawlyn Charlotte C Kaiser Martin F MF Johnson David C DC Qiang Ya-Wei YW Jones John R JR Cairns David A DA Gregory Walter M WM Owen Roger G RG Cook Gordon G Drayson Mark T MT Jackson Graham H GH Davies Faith E FE Morgan Gareth J GJ

Nature communications 20150423

We have sequenced 463 presenting cases of myeloma entered into the UK Myeloma XI study using whole exome sequencing. Here we identify mutations induced as a consequence of misdirected AID in the partner oncogenes of IGH translocations, which are activating and associated with impaired clinical outcome. An APOBEC mutational signature is seen in 3.8% of cases and is linked to the translocation-mediated deregulation of MAF and MAFB, a known poor prognostic factor. Patients with this signature have ...[more]

PMID: 25904160

Similar Datasets

463 newly diagnosed patients with Multiple Myeloma underwent whole exome sequencing of tumour and peripheral blood DNA.

Project description:463 newly diagnosed patients from the UK Myeloma XI clinical trial (NCT01554852) underwent whole exome sequencing plus targeted capture of the IGH/K/L and MYC loci. 200 ng of DNA were processed using NEBNext DNA library prepartion kit and hybridised to the SureSelect Human All Exon V5 Plus. Four samples were pooled and run on one lane of a HiSeq 2000 using 76-bp paired end reads. DNA from CD138+ selected bone marrow cells (myeloma tumour) as well as peripheral white blood cells were analysed and somatic mutations detected.

| EGAS00001001147 | EGA

2f022d00-f5f7-47b6-8fed-e5df11c0a7f7 - samples

Project description:The dataset contains WGS and RNA-seq from Myeloma XI trial

| EGAD00001005491 | EGA

ena-DATASET-UAMS-09-05-2018-19:35:00:131-1808 - samples

Project description:DNA (n=1281) and RNA (n=767) were extracted from bone marrow aspirates where CD138+ selection had been performed to enrich plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM). DNA and/or RNA were sent to Foundation Medicine where targeted sequencing was performed using their Foundation 1 Heme panel. Resulting BAM files were returned along with annotations for somatic events including single nucleotide mutations, indels and structural rearrangements.

| EGAD00001004113 | EGA

ArrayCGH profiling of two B-cell lineage subpopulations in multiple myeloma

Project description:ArrayCGH profiling and examination of IgH disruption by FISH on two myeloma B-cell lineage subpopulations: CD138+ and CD19+ to confirm existence of abnormal bone marrow B-cell subset contaning genetic background for primary oncogenic events.

2013-12-07 | E-MTAB-1401 | biostudies-arrayexpress

MMSET regulates transcription factors critical for survival of t(4;14) myeloma myeloma cells

Project description:Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. The multiple myeloma SET domain (MMSET), identified by its fusion to the IgH locus in t(4;14) MM, is universally overexpressed and has been suggested to play an important role in tumorigenicity in t(4;14) MM. In order to identify downstream functional targets of MMSET, we knocked down MMSET expression with shRNAs in KMS11, a t(4;14) MM cell line, and identified differentially expressed genes by gene expression microarray analysis.

2014-07-16 | GSE59424 | GEO

Effect of DNA extraction method on brain DNA copy number estimation

Project description:We analysed DNA from two brain regions (cerebellum, CER and frontal cortex, FC) from 4 Parkinson's disease (PD) and 4 control brains on a custom design 8x60k Agilent aCGH targeted to PD genes. All brain DNA samples were hybridised with Agilent sex-matched reference DNA, and three CER samples were hybridised against the FC of the same brain, with a dye swap in one. Male and female reference DNA were hybridised to eachother. The samples were then re-extracted with additional protocols, and hybridisations were performed for two CER samples betwen DNA extracted from the same CER with different protocols, and for one brain between the CER and FC new extraction.

2016-02-01 | GSE71360 | GEO

A high-throughput small molecule screen identifies synergism between DNA methylation and Aurora kinase pathways for X-chromosome reactivation

Project description:X-chromosome inactivation is a mechanism of dosage compensation in which one of the two X chromosomes in female mammals is transcriptionally silenced. Once established, silencing of the inactive X (Xi) is robust and difficult to reverse pharmacologically. Yet, the Xi is a reservoir of >1000 functional genes that could be potentially tapped to treat X-linked disease. To identify compounds that could reactivate the Xi, here we screened ~367,000 small molecules in an automated high-content screen using an Xi-linked GFP reporter in mouse fibroblasts. Given the robust nature of silencing, we sensitized the screen by “priming” cells with the DNA methyltransferase inhibitor, 5-aza-2’-deoxycytidine (5azadC). Compounds that elicited GFP activity include VX680, MLN8237, and 5azadC,, which are known to target the Aurora kinase and DNA methylation pathways. We demonstrate that the combinations of VX680 and 5azadC, as well as MLN8237 and 5azadC, synergistically upregulated genes on the Xi. Thus, our work identifies a synergism between the DNA methylation and Aurora kinase pathways as being one of interest for possible pharmacological reactivation of the Xi.

2017-02-10 | GSE85103 | GEO

The BET bromodomain inhibitor CPI203 improves lenalidomide activity in in vitro and in vivo models of multiple myeloma by synergistic blockade of Ikaros and c-Myc signaling

Project description:Multiple myeloma (MM) cells were treated with the BET inhibitor CPI203 alone and in combination with lenalidomide plus dexamethasone in vitro and in vivo (mouse xenograft). We used microarrays to uncover the mechanisms underlying CPI-203 activity in MM, alone and in combination with lenalidomide plus dexamethasone (combo).

2016-09-28 | GSE87403 | GEO

Myeloma WGS

Project description:Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80 tumour-normal newly diagnosed pairs and 24 matched relapse tumours from the Myeloma XI trial.

| EGAS00001004000 | EGA

RNA-seq of Multiple Myeloma

Project description:Purpose: Multiple myeloma is a malignancy of plasma cells. Extensive genetic and transcriptional characterization of myeloma has identified subtypes with prognostic and therapeutic implications. In contrast, relatively little is known about the myeloma epigenome. Experimental Design: CD138+CD38+ myeloma cells were isolated from fresh bone marrow aspirate or the same aspirate after freezing for one to six months. Gene expression and chromatin accessibility were compared between fresh and frozen samples by RNA-seq and ATAC-seq. Chromatin accessible regions were used to identify regulatory RNA expression in over 700 samples from newly diagnosed patients in the MMRF CoMMpass trial (NCT01454297). Results: Gene expression and chromatin accessibility of cryopreserved myeloma recapitulated that of freshly isolated samples. ATAC-seq performed on a series of biobanked specimens identified thousands of chromatin accessible regions with hundreds being highly coordinated with gene expression. Over 4,700 of these chromatin accessible regions were transcribed in newly diagnosed myelomas from the CoMMpass trial. Regulatory element activity alone recapitulated myeloma gene expression subtypes, and in particular myeloma subtypes with IGH translocations were defined by transcription of distal regulatory elements. Moreover, enhancer activity predicted oncogene expression implicating gene regulatory mechanisms in aggressive myeloma. Conclusions: These data demonstrate the feasibility of using biobanked specimens for retrospective studies of the myeloma epigenome and illustrate the unique enhancer landscapes of myeloma subtypes that are coupled to gene expression and disease progression.

2021-03-03 | GSE167968 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data