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  • Volume Number 7
  •  Issue 4
    • Cover Date: January 01, 2007


Sequential Analysis of Chromosome Aberrations in Multiple Myeloma During Disease Progression


Authors: Ka Lung Wu, Berna Beverloo, Sandra J. C. M. Velthuizen, Pieter Sonneveld

Purpose: Several chromosomal aberrations have been associated with molecular pathogenesis and classification of multiple myeloma. It is not known whether the expression of abnormal karyotypes is consistent in patients during disease progression. Herein, we report on sequential analysis of conventional cytogenetics as well as fluorescence in situ hybridization (FISH) data of 79 bone marrow specimens from 38 patients with myeloma who were longitudinally followed. Patients and Methods: We determined and characterized the development of additional chromosomal aberrations during progressive disease. Results: Overall, conventional cytogenetics detected an abnormal karyotype in 42% of the samples, whereas this increased to 69% by FISH. Among the cases with an abnormal conventional karyotype, 52% had a hyperdiploid subtype of myeloma. Progressive disease was correlated with an increased complexity of genetic abnormalities, which in the majority, consisted of structural aberrations acquired in later stages of disease. Using conventional cytogenetics, rearrangements of chromosome 1 were the most common structural abnormality (15%). In the majority, these rearrangements consisted of unbalanced translocations of 1p and 1q; however, no specific locus was predominantly affected. Second in frequency were structural aberrations of chromosomes 8 and 17 (6%). The frequency of del(13q) by FISH was 40% and did not increase in later stages of the disease, suggesting that del(13q) is not a genetic event associated with disease progression. Change of ploidy category during disease progression occurred in a minority of the cases. Conclusion: This study supports the notion that cytogenetic abnormalities in multiple myeloma are not random. Particular chromosomal alterations are associated with disease progression, whereas others show a stable pattern during the course of the disease.

Keywords: Chromosome 1, Clonal evolution, Cytogenetics, Fluorescence in situ hybridization


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