The prognostic significance of cytogenetics and molecular profiling in multiple myeloma

被引:154
作者
Sawyer, Jeffrey R. [1 ,2 ]
机构
[1] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA
[2] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA
关键词
Multiple myeloma; cytogenetics; molecular profiling; prognosis; IN-SITU HYBRIDIZATION; COMPARATIVE GENOMIC HYBRIDIZATION; PLASMA-CELL LEUKEMIA; CHROMOSOME BAND 1Q21; P53; GENE-MUTATIONS; HIGH-DOSE THERAPY; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; PERICENTROMERIC HETEROCHROMATIN; JUMPING TRANSLOCATIONS;
D O I
10.1016/j.cancergencyto.2010.11.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3 / 12
页数:10
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