Hypodiploid multiple myeloma is characterized by more aggressive molecular markers than non-hyperdiploid multiple myeloma

Scott Van Wier, Esteban D Braggio, Angela Baker, Gregory Ahmann, Joan Levy, John D. Carpten, Rafael Fonseca

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Multiple myeloma can be categorized into hyperdiploid or non-hyperdiploid myeloma based on the number of chromosomes found in the tumor clone. Among the non-hyperdiploid myelomas, the hypodiploid subtype has the most aggressive clinical phenotype, but the genetic differences between groups are not completely defined. In order to understand the genetic background of hypodiploid multiple myeloma better, we compared the genomic (array-based comparative genomic hybridization) and transcriptomic (gene expression profiling) background of 49 patients with hypodiploid myeloma with 50 other non-hyperdiploid and 125 hyperdiploid myeloma patients. There were significant chromosomal and gene expression differences between hyperdiploid patients and nonhyperdiploid and hypodiploid patients. Non-hyperdiploid and hypodiploid patients shared most of the chromosomal abnormalities; nevertheless a subset of these abnormalities, such as monosomies 13, 14 and 22, was markedly increased in hypodiploid patients. Furthermore, deletions of 1p, 12p, 16q and 17p, all associated with poor outcome or progression in multiple myeloma, were significantly enriched in hypodiploid patients. Molecular risk-stratification indices reinforce the worse prognosis associated with hypodiploid multiple myeloma compared with non-hyperdiploid multiple myeloma. Gene expression profiling clustered hypodiploid and non-hyperdiploid subgroups closer than hyperdiploid myeloma but also highlighted the up-regulation of CCND2, WHSC1/MMSET and FGFR3 in the hypodiploid subtype. In summary, hypodiploid multiple myeloma is genetically similar to nonhyperdiploid multiple myeloma but characterized by a higher prevalence of genetic alterations associated with poor outcome and disease progression. It is provocative to hypothesize that hypodiploid multiple myeloma is an advanced stage of non-hyperdiploid multiple myeloma.

Original languageEnglish (US)
Pages (from-to)1586-1592
Number of pages7
JournalHaematologica
Volume98
Issue number10
DOIs
StatePublished - Oct 1 2013

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Multiple Myeloma
Polyploidy
Gene Expression Profiling
Monosomy
Comparative Genomic Hybridization
Chromosome Aberrations
Disease Progression
Up-Regulation
Clone Cells
Chromosomes
Phenotype
Gene Expression

ASJC Scopus subject areas

  • Hematology

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Hypodiploid multiple myeloma is characterized by more aggressive molecular markers than non-hyperdiploid multiple myeloma. / Van Wier, Scott; Braggio, Esteban D; Baker, Angela; Ahmann, Gregory; Levy, Joan; Carpten, John D.; Fonseca, Rafael.

In: Haematologica, Vol. 98, No. 10, 01.10.2013, p. 1586-1592.

Research output: Contribution to journalArticle

Van Wier, Scott ; Braggio, Esteban D ; Baker, Angela ; Ahmann, Gregory ; Levy, Joan ; Carpten, John D. ; Fonseca, Rafael. / Hypodiploid multiple myeloma is characterized by more aggressive molecular markers than non-hyperdiploid multiple myeloma. In: Haematologica. 2013 ; Vol. 98, No. 10. pp. 1586-1592.
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abstract = "Multiple myeloma can be categorized into hyperdiploid or non-hyperdiploid myeloma based on the number of chromosomes found in the tumor clone. Among the non-hyperdiploid myelomas, the hypodiploid subtype has the most aggressive clinical phenotype, but the genetic differences between groups are not completely defined. In order to understand the genetic background of hypodiploid multiple myeloma better, we compared the genomic (array-based comparative genomic hybridization) and transcriptomic (gene expression profiling) background of 49 patients with hypodiploid myeloma with 50 other non-hyperdiploid and 125 hyperdiploid myeloma patients. There were significant chromosomal and gene expression differences between hyperdiploid patients and nonhyperdiploid and hypodiploid patients. Non-hyperdiploid and hypodiploid patients shared most of the chromosomal abnormalities; nevertheless a subset of these abnormalities, such as monosomies 13, 14 and 22, was markedly increased in hypodiploid patients. Furthermore, deletions of 1p, 12p, 16q and 17p, all associated with poor outcome or progression in multiple myeloma, were significantly enriched in hypodiploid patients. Molecular risk-stratification indices reinforce the worse prognosis associated with hypodiploid multiple myeloma compared with non-hyperdiploid multiple myeloma. Gene expression profiling clustered hypodiploid and non-hyperdiploid subgroups closer than hyperdiploid myeloma but also highlighted the up-regulation of CCND2, WHSC1/MMSET and FGFR3 in the hypodiploid subtype. In summary, hypodiploid multiple myeloma is genetically similar to nonhyperdiploid multiple myeloma but characterized by a higher prevalence of genetic alterations associated with poor outcome and disease progression. It is provocative to hypothesize that hypodiploid multiple myeloma is an advanced stage of non-hyperdiploid multiple myeloma.",
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