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| 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
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| 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.
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.
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| Overall design |
[SNP genotyping] 24 myeloma patients at diagnosis and relapse examined with high resolution genome-wide chip
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| 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 |
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| 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 |
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| Samples (76)
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| This SubSeries is part of SuperSeries: |
| GSE37469 |
Minor clone provides a reservoir for relapse in multiple myeloma |
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| Relations |
| BioProject |
PRJNA134695 |
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