Inserm U892, Université de Nantes, Nantes, France.
Blood. 2011 Jul 21;118(3):675-8. doi: 10.1182/blood-2011-03-344069. Epub 2011 May 31.
Multiple myeloma (MM) develops from a premalignant plasma cell proliferative disorder, and with time can progress to a more aggressive disease in extramedullary locations. The gradually clinical evolution is supported by clonal expansion of cells that acquire genetic lesions over years. This model of cancer evolution based on ongoing genomic instability mechanism may apply to development of most MM cases. However, in a small fraction of newly diagnosed MM who relapse quickly and finally die within 2 years, the gradual model appears to be untenable. Analysis of high resolution copy number profiles obtained using single nucleotide polymorphism array data from 764 newly diagnosed MM identified large numbers of genomic rearrangements with the hallmarks of chromothripsis in 1.3% of samples. Moreover, this catastrophic event confers a poor outcome. Because chromothripsis appears to occur in a single crisis, our results suggest that high-risk MM patients use this novel way of cancer evolution.
多发性骨髓瘤（MM）源于恶性前浆细胞增生性疾病，随着时间的推移，可进展为骨髓外部位侵袭性更强的疾病。这种以不断发生的基因组不稳定性机制为基础的癌症演进模式可能适用于大多数 MM 病例的发生发展。然而，在一小部分新诊断的 MM 患者中，其疾病迅速复发，并在 2 年内最终死亡，这种逐渐演进的模式似乎难以成立。对 764 例新诊断 MM 患者使用单核苷酸多态性阵列数据获得的高分辨率拷贝数谱进行分析，在 1.3%的样本中发现了大量具有染色体重排特征的基因组重排。此外，这种灾难性事件预示着不良预后。由于染色体重排似乎发生在单一危机中，因此我们的研究结果提示高危 MM 患者可能使用这种新颖的癌症演进方式。
