Analysis of genetic abnormalities provides insights into genetic evolution of hyperdiploid myeloma

Wee J. Chng, Rhett P. Ketterling, Rafael Fonseca

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 bio-logical relevance. Within this framework, we propose a model of genetic evolution in H-MM.

Original languageEnglish (US)
Pages (from-to)1111-1120
Number of pages10
JournalGenes Chromosomes and Cancer
Volume45
Issue number12
DOIs
StatePublished - Dec 2006

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Polyploidy
Molecular Evolution
Chromosomes
Genomic Instability
Aneuploidy
Karyotype
Monosomy
Neoplasms
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 3
Loss of Heterozygosity
Trisomy
Clone Cells

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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Analysis of genetic abnormalities provides insights into genetic evolution of hyperdiploid myeloma. / Chng, Wee J.; Ketterling, Rhett P.; Fonseca, Rafael.

In: Genes Chromosomes and Cancer, Vol. 45, No. 12, 12.2006, p. 1111-1120.

Research output: Contribution to journalArticle

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