Multiple myeloma patients are mainly categorized into hyperdiploid or non- hyperdiploid myeloma based on the number of chromosomes found in the tumor clone. Among non-hyperdiploid patients the hypodiploid subtype has the most aggressive clinical phenotype, but the genetic differences between groups are not completely defined. In order to better understand the genetic background of hypodiploid multiple myeloma, we compared the genomic (array-based comparative genomic hybridization) and transcriptomic (gene expression profiling) background of 49 hypodiploid with 50 other non-hyperdiploid and 125 hyperdiploid myeloma patients. Hyperdiploid patients showed significant chromosomal and gene expression differences with non-hyperdiploid and hypodiploid patients. Non-hyperdiploid and hypodiploid patients shared most of the chromosomal abnormalities; nevertheless a subset of these abnormalities was markedly increased in hypodiploid patients such as monosomies 13, 14 and 22. 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 than in 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 is genetically similar to non-hyperdiploid multiple myeloma but characterized by 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.
- Received November 8, 2012.
- Accepted May 9, 2013.
- Copyright © 2013, Ferrata Storti Foundation