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Series GSE25262 Query DataSets for GSE25262
Status Public on Feb 13, 2013
Title Genetic adaptability of cancer cells under treatment selection pressure in multiple myeloma patients.
Organism Homo sapiens
Experiment type SNP genotyping by SNP array
Genome variation profiling by SNP array
Summary 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.


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.


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.
Overall design [SNP genotyping] 24 myeloma patients at diagnosis and relapse examined with high resolution genome-wide chip
Contributor(s) Magrangeas F, Avet-Loiseau H, Decaux O, Gouraud W, Anderson KC, Moreau P, Munshi NC, Minvielle S
Citation(s) 22874878
Submission date Nov 10, 2010
Last update date Nov 27, 2018
Contact name Wilfried Gouraud
Organization name ICO - UMGC
Department Integrated Center of Oncology René Gauducheau
Lab Omics Data Science Unit
Street address bd Jacques Monod
City Saint Herblain
ZIP/Postal code 44805
Country France
Platforms (3)
GPL3718 [Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array
GPL3720 [Mapping250K_Sty] Affymetrix Mapping 250K Sty2 SNP Array
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (76)
GSM621360 MM_#03
GSM621361 MM_#03R
GSM621362 MM_#03R_blood
This SubSeries is part of SuperSeries:
GSE37469 Minor clone provides a reservoir for relapse in multiple myeloma
BioProject PRJNA134695

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE25262_RAW.tar 2.2 Gb (http)(custom) TAR (of CEL)
GSE25262_patientID_treatment.txt.gz 346 b (ftp)(http) TXT
Processed data included within Sample table

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