Sawyer JR.
Department of Pathology and Myeloma Institute
for Research and Therapy, University of Arkansas
for Medical Sciences, Little Rock, AR, USA.
sawyerjeffreyr@uams.edu
Abstract
Multiple myeloma (MM) is a plasma cell
malignancy characterized by very complex
cytogenetic and molecular genetic aberrations.
In newly diagnosed symptomatic patients, the
modal chromosome number is usually either
hyperdiploid with multiple trisomies or
hypodiploid with one of several types of
immunoglobulin heavy chain (Ig) translocations.
The chromosome ploidy status and Ig
rearrangements are two genetic criteria that are
used to help stratify patients into prognostic
groups based on the findings of conventional
cytogenetics and fluorescence in situ
hybridization (FISH). In general, the
hypodiploid group with t(4;14)(p16;q32) or
t(14;16)(q32;q23) is considered a high-risk
group, while the hyperdiploid patients with
t(11;14)(q13;q32) are considered a better
prognostic group. As the disease progresses, it
becomes more proliferative and develops a number
of secondary chromosome aberrations. These
secondary aberrations commonly involve MYC
rearrangements, del(13q), del(17p), and the
deletion of 1p and/or amplification of 1q. Of
the secondary aberrations, del(17p) is
consistently associated with poor prognosis. All
of these cytogenetic aberrations and many
additional ones are now identified by means of
high resolution molecular profiling. Gene
expression profiling (GEP), array comparative
genomic hybridization (aCGH), and
single-nucleotide polymorphism (SNP) arrays have
been able to identify novel genetic aberration
patterns that have previously gone unrecognized.
With the integration of data from these
profiling techniques, new subclassifications of
MM have been proposed which define distinct
molecular genetic subgroups. In this review, the
findings from conventional cytogenetics,
interphase FISH, GEP, aCGH, and SNP profiles are
described to provide the conceptual framework
for defining the emerging molecular genetic
subgroups with prognostic significance.
Copyright © 2011 Elsevier Inc. All rights
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