Document Detail


Prognostic significance of copy-number alterations in multiple myeloma.
MedLine Citation:
PMID:  19687334     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown.
PATIENTS AND METHODS: 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.
RESULTS: Our analyses revealed deletions and amplifications in 98% of patients. Amplifications in 1q and deletions in 1p, 12p, 14q, 16q, and 22q were the most frequent lesions associated with adverse prognosis, whereas 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), del(17p), and serum beta(2)-microglobulin [Sbeta(2)M]), del(12p13.31) remained the most powerful independent adverse marker (P < .0001; hazard ratio [HR], 3.17) followed by Sbeta(2)M (P < .0001; HR, 2.78) and the favorable marker amp(5q31.3) (P = .0005; HR, 0.37). Patients with amp(5q31.3) alone and low Sbeta(2)M had an excellent prognosis (5-year overall survival, 87%); conversely, patients with del(12p13.31) alone or amp(5q31.3) and del(12p13.31) and high Sbeta(2)M had a very poor outcome (5-year overall survival, 20%). This prognostic model was validated in an independent validation cohort of 273 patients with myeloma.
CONCLUSION: These findings demonstrate the power and accessibility of molecular karyotyping to predict outcome in myeloma. In addition, integration of expression of genes residing in the lesions of interest revealed putative features of the disease driving short survival.
Authors:
Hervé Avet-Loiseau; Cheng Li; Florence Magrangeas; Wilfried Gouraud; Catherine Charbonnel; Jean-Luc Harousseau; Michel Attal; Gerald Marit; Claire Mathiot; Thierry Facon; Philippe Moreau; Kenneth C Anderson; Loïc Campion; Nikhil C Munshi; Stéphane Minvielle
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-08-17
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  27     ISSN:  1527-7755     ISO Abbreviation:  J. Clin. Oncol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-10-02     Completed Date:  2009-11-04     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4585-90     Citation Subset:  IM    
Affiliation:
L'Institut National de la Santé et de la Recherche Médicale U892, Université de Nantes, Institut de Biologie, 9 Quai Moncousu, Nantes, 44093, France.
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MeSH Terms
Descriptor/Qualifier:
Chromosome Aberrations
Gene Dosage*
Humans
Multiple Myeloma / genetics*
Polymorphism, Single Nucleotide
Predictive Value of Tests
Prognosis
Grant Support
ID/Acronym/Agency:
P01-78378//PHS HHS; P50 CA100707-04/CA/NCI NIH HHS; R01 CA124929-05/CA/NCI NIH HHS; R01-129295//PHS HHS; R01-50947//PHS HHS
Comments/Corrections
Comment In:
J Clin Oncol. 2011 Jan 10;29(2):e37-9; author reply e40-1   [PMID:  21135272 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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