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| Status |
Public on Aug 20, 2009 |
| Title |
Prognostic significance of copy-number alterations in multiple myeloma |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
SNP genotyping by SNP array
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| Summary |
Purpose
Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown.
Methods
We performed a genome-wide analysis of malignant plasma cells from 192 newly myeloma patients using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis.
Results
Our analyses revealed deletions and amplifications in 98% of cases. Amplifications in 1q and deletions in 1p, 12p, 14q, 16q, and 22q were the most frequent lesions associated with adverse prognosis while recurrent amplifications of chromosomes 5, 9, 11, 15 and 19 conferred a favorable prognosis.
Multivariate analysis retained three independent lesions: amp(1q23.3), amp(5q31.3) and del(12p13.31). When adjusted to the established prognostic variables ie t(4;14), and serum beta2-microglobulin (Sb2M), del(12p13.31) remained the most powerful independent marker (P <.0001; hazard ratio = 3.17) followed by Sb2M (P <.0001; hazard ratio = 2.78) and amp(5q31.3) (P =.0005; hazard ratio = 0.37). Cases with amp(5q31.3) alone and low Sb2M had an excellent prognosis (5-year overall survival = 87%) conversely cases with del(12p13.31) alone or amp(5q31.3) and del(12p13.31) and high Sb2M had a very poor outcome (5-year overall survival = 20%). Moreover, integration of SNP mapping and gene expression identified CD27 as potential critical gene responsible for poor prognosis of del(12p) myeloma patients.
Conclusion
These findings demonstrate the power and accessibility of molecular karyotyping to identify novel strong independent prognostic markers: amp(5q31.3) and del(12p13.31) and to provide insights into putative pathways deregulated in sub classes of cancer patients.
Keywords: Human chromosome copy-number alterations study
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| Overall design |
192 myeloma patients at diagnosis examined with 500K Set Affymetrix chips
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| Contributor(s) |
Avet-Loiseau H, Li C, Magrangeas F, Gouraud W, Charbonnel C, Harousseau J, Attal M, Marit G, Mathiot C, Facon T, Moreau P, Anderson KC, Campion L, Munshi NC, Minvielle S |
| Citation(s) |
19687334, 37611163 |
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| Submission date |
Sep 23, 2008 |
| Last update date |
Dec 07, 2023 |
| Contact name |
Wilfried Gouraud |
| Organization name |
ICO - UMGC
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| Department |
Integrated Center of Oncology René Gauducheau
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| Lab |
Omics Data Science Unit
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| Street address |
bd Jacques Monod
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| City |
Saint Herblain |
| ZIP/Postal code |
44805 |
| Country |
France |
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| Platforms (2) |
| GPL3718 |
[Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array |
| GPL3720 |
[Mapping250K_Sty] Affymetrix Mapping 250K Sty2 SNP Array |
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| Samples (384)
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| Relations |
| BioProject |
PRJNA110893 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12896_RAW.tar |
10.4 Gb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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