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Prognostic significance of copy-number alterations in multiple myeloma


ABSTRACT: 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 192 myeloma patients at diagnosis examined with 500K Set Affymetrix chips

ORGANISM(S): Homo sapiens

SUBMITTER: Wilfried Gouraud 

PROVIDER: E-GEOD-12896 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Prognostic significance of copy-number alterations in multiple myeloma.

Avet-Loiseau Hervé H   Li Cheng C   Magrangeas Florence F   Gouraud Wilfried W   Charbonnel Catherine C   Harousseau Jean-Luc JL   Attal Michel M   Marit Gerald G   Mathiot Claire C   Facon Thierry T   Moreau Philippe P   Anderson Kenneth C KC   Campion Loïc L   Munshi Nikhil C NC   Minvielle Stéphane S  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20090817 27


<h4>Purpose</h4>Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown.<h4>Patients and methods</h4>We performed a genome-wide analysis of malignant plasma cells from 192 newly diagnosed patients with myeloma using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis.<h4>Results</h4>Our analyses revealed deletions and amplifications in 98% of patients. Amplifications in 1q and del  ...[more]

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