Prognostic significance of copy-number alterations in multiple myeloma.
OBJECTIVE
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 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.


CONCLUSIONS
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.
Avet-Loiseau
Hervé
H
L'Institut National de la Santé et de la Recherche Médicale U892, Université de Nantes, Institut de Biologie, 9 Quai Moncousu, Nantes, 44093, France.
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
D002869:Chromosome Aberrations; D018628:Gene Dosage; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis
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