Haematologica. 2013 Oct;98(10):1586-92. doi: 10.3324/haematol.2012.081083. Epub 2013 May 28.
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 non-hyperdiploid 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 non-hyperdiploid 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.
多发性骨髓瘤可以根据肿瘤克隆中发现的染色体数量分为超二倍体或非超二倍体骨髓瘤。在非超二倍体骨髓瘤中，亚二倍体亚型具有最具侵袭性的临床表型，但各组之间的遗传差异尚未完全确定。为了更好地了解亚二倍体多发性骨髓瘤的遗传背景，我们比较了 49 例亚二倍体骨髓瘤患者、50 例非超二倍体和 125 例超二倍体骨髓瘤患者的基因组（基于阵列的比较基因组杂交）和转录组（基因表达谱分析）背景。超二倍体患者与非超二倍体和亚二倍体患者之间存在显著的染色体和基因表达差异。非超二倍体和亚二倍体患者共享大多数染色体异常；然而，这些异常中的一部分，如 13、14 和 22 号单体，在亚二倍体患者中明显增加。此外，与多发性骨髓瘤不良预后或进展相关的 1p、12p、16q 和 17p 缺失在亚二倍体患者中显著富集。分子风险分层指数进一步强化了与非超二倍体多发性骨髓瘤相比，亚二倍体多发性骨髓瘤预后更差的结论。基因表达谱分析将亚二倍体和非超二倍体亚组聚类得比超二倍体骨髓瘤更接近，但也突出了亚二倍体亚型中 CCND2、WHSC1/MMSET 和 FGFR3 的上调。总之，亚二倍体多发性骨髓瘤在遗传上与非超二倍体多发性骨髓瘤相似，但具有更高的与不良预后和疾病进展相关的遗传改变发生率。假设亚二倍体多发性骨髓瘤是非超二倍体多发性骨髓瘤的晚期阶段，这是一个很有启发性的假说。
