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Expression of genetic adaptability of cancer cells under treatment selection pressure in multiple myeloma patients

ABSTRACT: Series GSE25262 patients on expression side. [Exon study] 11 myeloma patients at diagnosis and relapse examined with Exon expression chip

ORGANISM(S): Homo sapiens

SUBMITTER: Wilfried Gouraud

PROVIDER: E-GEOD-37414 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Minor clone provides a reservoir for relapse in multiple myeloma.

Magrangeas F F Avet-Loiseau H H Gouraud W W Lodé L L Decaux O O Godmer P P Garderet L L Voillat L L Facon T T Stoppa A M AM Marit G G Hulin C C Casassus P P Tiab M M Voog E E Randriamalala E E Anderson K C KC Moreau P P Munshi N C NC Minvielle S S

Leukemia 20120809 2

Recent studies have provided direct evidence for genetic variegation in subclones for various cancer types. However, little is known about subclonal evolutionary processes according to treatment and subsequent relapse in multiple myeloma (MM). This issue was addressed in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. As MM is a highly heterogeneous disease associated with a large number of chromosomal abnormalities, a subset ...[more]

PMID: 22874878

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Minor clone provides a reservoir for relapse in multiple myeloma

Project description:In this study we addressed subclonal evolutionary process after treatment and subsequent relapse in multiple myeloma (MM) in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. Because MM is a highly heterogeneous disease coupled with a large number of DNA copy number alterations (CNAs) and loss of heterozygosity (LOH), we focused our study on the secondary genetic events: 1q21 gain, NF-kB activating mutations, RB1 and TP53 deletions, that seem to reflect progression. By using genome-wide high resolution SNP arrays we identified subclones with nonlinear complex evolutionary histories in a third of patients with myeloma, the relapse clone apparently derived from a minor subclone at diagnosis. Such reordering of the spectrum of genetic lesions during therapy is likely to reflect selection of genetically distinct subclones not initially competitive against the dominant population that survived chemotherapy, thrived and acquired new anomalies. In addition we found that emergence of minor subclones at relapse was significantly associated with bortezomib treatment. Altogether, these data support the idea of new strategy of future clinical trials in MM that would combine targeted therapy and subpopulations control to eradicate all myeloma subclones in order to obtain long-term remission. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-02-13 | E-GEOD-37469 | biostudies-arrayexpress

Gene Expression profiling of Multiple Myeloma

Project description:Gene Expression profiling of 170 newly diagnosed Multiple Myeloma patients Gene Expression profiling of Multiple Myeloma Cells from Healthy donors and Multiple myeloma patients were profiled using Affymetrix Exon-1.0 ST microarrays

2012-09-10 | E-GEOD-39754 | biostudies-arrayexpress

A Systematic Comparison and Evaluation of High Density Exon Arrays and RNA-seq technology in Unraveling the Peripheral Blood Transcriptome of Sickle Cell Disease.

Project description:Sickle cell transcriptome was analyzed using whole blood clinical specimens on the Affymetrix Human Exon 1.0 ST arrays and Illumina’s deep sequencing technologies. Data analysis indicated a strong concordance (R=0.64) between exon array and RNA-seq in both gene level and exon level expression of transcripts. The magnitude of fold changes in the expression levels for the differentially expressed genes (p<0.05) was found to be higher in RNA-seq than microarrays. However, the arrays outperformed the sequencing technology in the detection of low abundant transcripts. In addition to examining the expression level changes of transcripts, RNA-seq technology was able to identify sequence variation in the expressed transcripts. We also demonstrate herein the ability of RNA-seq technology to discover novel expression outside of the annotated genes. This Series contains only the Exon array data. 10 patients and 10 healthy subjects participated in this study. Gene chip experiments were carreid out on 6 patients and 4 healthy controls Human Exon 1.0 ST Arrays

2012-07-05 | E-GEOD-31757 | biostudies-arrayexpress

ENCODE Tier2 cell phenotyping study

Project description:These samples are part of the ENCODE consortium’s proposed time-limited Pilot Study for confirmation of the utility of RNA abundance measurements as a standard reference phenotyping tool. Keywords: cell type comparison For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Each of the 7 ENCODE laboratories submitted biological triplicates for at least one of the four Tier2 cell lines. These were processed on Affymetrix Exon 1.0 ST arrays to obtain phenotyping data for each cell ine.

2009-08-24 | E-GEOD-17778 | biostudies-arrayexpress

Comparative transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) isolated from patients in secondary prevention of CVD taking placebo, grape extract or resveratrol-enriched grape extract

Project description:We used Affymetrix microarrays to investigate gene expression changes in PBMCs isolated from male patients ongoing secondary prevention of CVD to determine significant modulatory effects that may have been induced by the intake of an initial dose of 8 mg of resveratrol-enriched grape extract for 6 months and then, 16 mg for a further 6 months. The aim of this work was to determine whether the daily intake of dietary levels of resveratrol (RES) for a total of 12 months exerted any modulatory effects, at the level of gene expression, in PBMCs isolated from patients in secondary prevention of CVD. Male patients were divided in 3 groups: placebo (A), grape extract (B) and resveratrol-enriched grape extract (C). Total RNA was extracted from isolated PBMCs belonging to a total of 18 diabetic male patients (6 from each group) in 3 time points (at day 0, after 6 months and after 12 months) to compare differential gene expression between the groups. Differential gene expression after 6 and 12 months of the study for each group: placebo (A), grape extract (B) and resveratrol-enriched grape extract (C)

2012-06-29 | E-GEOD-36930 | biostudies-arrayexpress

Genetic adaptability of cancer cells under treatment selection pressure in multiple myeloma patients.

Project description:Purpose Despite advances and significant improvement in survival, multiple myeloma (MM) remains incurable and nearly all patients relapse after treatment. Previous studies have shown a complex spectrum of diverse genetic alterations in almost all patients, but evolution of genomic rearrangements throughout myeloma life cycle has not been investigated. Patients and Methods We performed genomic analysis integrating copy number, allele specific copy number, allele ratio calculations, breakpoint sequencing and rearrangement PCR genotyping on matched diagnosis and relapse samples from 24 MM patients either treated with proteasome inhibitor (bortezomib)-based induction regimen or conventional chemotherapeutic agents. Results All relapse samples have a clear relationship to the diagnosis clone with significant increase of copy number abnormalities (CNAs). Despite a wide diversity of CNAs acquired at relapse, regulators of NF-kB activity were targeted in 25% of the patients. Relapse-associated lesions either appeared as new acquisition or were selected from minor subpopulations at diagnosis. In one third of the patients, we found loss of abnormities containing loss of heterozygosity (LOH) providing evidence that the relapse clone derived from an ancestral clone shared with the dominant diagnosis clone. Remarkably, re-emergence of ancestral clones was almost exclusively found in patients treated with bortezomib, attested to a remarkable adaptability of myeloma cells under targeted drug selection pressure. Conclusion These data suggest that genomic instability and clonal selection are the main forces that drive adaptive changes in MM under drug selection pressure, and they support the proposal to combine several anti-myeloma drugs upfront in order to obtain long-term remissions. [SNP genotyping] 24 myeloma patients at diagnosis and relapse examined with high resolution genome-wide chip

2013-02-13 | E-GEOD-25262 | biostudies-arrayexpress

Genetic adaptability of cancer cells under treatment selection pressure in multiple myeloma patients.

2013-02-13 | GSE25262 | GEO

Exon-level expression profiling of normal colonic mucosa samples.

Project description:These samples have been analyzed for global alternative splicing variation on exon-level expression data using the FIRMA algorithm. We have identified and described transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of solid cancers. This Series consists of 19 normal colonic mucosa samples from colorectal cancer patients, and is an amendment to a larger series of colorectal cancer and adjacent normal colonic mucosa samples analyzed for gene expression at the exon-level (GSE24550).

2014-08-13 | E-GEOD-42690 | biostudies-arrayexpress

Exon-level analyses of neuroblastoma

Project description:In this study, mRNA expression profiles of 113 primary untreated human neuroblastoma samples were compared with the aim to identify prognostic exon and gene sets as well as parameters associated with alternative exon use. The primary neuroblastoma specimens were from tumor banks in Cologne or Essen, Germany, Ghent, Belgium and Valencia, Spain. All patients were diagnosed between 1998 and 2007 and treated according to the German Neuroblastoma trials NB97, NB 2004 or the SIOPEN protocol. This submission contains 87 exon array profiles and are used together with exon array data from 26 Samples in GSE21713 (see 'Relation' links below) to predict the outcome of patients with neuroblastoma. The resulting dataset, which is linked below as a supplementary file ('GSE32664_complete_RMA_data.txt'), was used for the subsequent analyses.

2012-06-17 | E-GEOD-32664 | biostudies-arrayexpress

Expression of genetic adaptability of cancer cells under treatment selection pressure in multiple myeloma patients

Project description:Series GSE25262 patients on expression side.

2013-02-13 | GSE37414 | GEO