Analysis of genetic abnormalities provides insights into genetic evolution of hyperdiploid myeloma
- 5 September 2006
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 45 (12), 1111-1120
- https://doi.org/10.1002/gcc.20375
Abstract
Aneuploidy is ubiquitous in human cancer and is seen as whole chromosome gains and losses, unbalanced translocations and inversions, duplications, deletions and loss of heterozygosity. Within this complexity, some subgroups of aneuploid tumors emerge as distinct biological and clinical entities. Hyperdiploid myeloma (H‐MM), characterized by hyperdiploid chromosome numbers because of nonrandom trisomies, is one such example. We undertook a comprehensive survey of the karyotypes of a large number of H‐MM (n = 469) to describe fully genomic instability in these tumors, to dissect pathways of genetic evolution, and identify distinct subgroups based on their genetic changes. While selective pressure apparently favors the emergence of clones with gains of chromosomes 3, 5, 7, 9, 11, 15, 19, and 21, a background of ongoing genomic instability results in gains of other chromosomes, albeit at a much lower prevalence. A deduced temporal analysis of these karyotypes indicates that selected gains are early events. Other events occurring later in the course of the disease include secondary chromosome translocations and monosomies. The development of these genetic aberrations is thus highly ordered and undoubtedly of biological relevance. Within this framework, we propose a model of genetic evolution in H‐MM.Keywords
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