|
| Status |
Public on Feb 13, 2013 |
| Title |
Minor clone provides a reservoir for relapse in multiple myeloma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Genome variation profiling by SNP array
SNP genotyping by SNP array
|
| Summary |
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.
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| Overall design |
Refer to individual Series
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| |
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| Contributor(s) |
Magrangeas F, Lodé L, Avet-Loiseau H, Decaux O, Gouraud W, Anderson KC, Moreau P, Munshi NC, Minvielle S |
| Citation(s) |
22874878 |
| |
| Submission date |
Apr 20, 2012 |
| Last update date |
Feb 18, 2019 |
| 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 (4)
|
| GPL3718 |
[Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array |
| GPL3720 |
[Mapping250K_Sty] Affymetrix Mapping 250K Sty2 SNP Array |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
| GPL6801 |
[GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array |
|
| Samples (99)
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| This SuperSeries is composed of the following SubSeries: |
| GSE25262 |
Genetic adaptability of cancer cells under treatment selection pressure in multiple myeloma patients. |
| GSE37414 |
Expression of genetic adaptability of cancer cells under treatment selection pressure in multiple myeloma patients |
|
| Relations |
| BioProject |
PRJNA160167 |
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