文章：

解析多发性骨髓瘤中拷贝数变异的时间顺序

Deciphering the chronology of copy number alterations in Multiple Myeloma

原文发布日期：2019-03-26

DOI: 10.1038/s41408-019-0199-3

类型: Article

开放获取: 是

英文摘要：

Multiple myeloma (MM) and its precursor condition MGUS are characterized by chromosomal aberrations. Here, we comprehensively characterize the order of occurrence of these complex genomic events underlying MM development using 500 MGUS, and MM samples. We identify hyperdiploid MM (HMM) and non-HMM as genomically distinct entities with different evolution of the copy number alterations. In HMM, gains of 9,15 or 19 are the first and clonal events observed as clonal even at MGUS stage. These events are thus early and may underlie initial transformation of normal plasma cells to MGUS cells. However, CNAs may not be adequate for progression to MM except in 15% of the patients in whom the complex subclonal deletion events are observed in MM but not MGUS. In NHMM, besides the driver translocations, clonal deletion of 13 and 1q gain are early events also observed in MGUS. We combined this information to propose a timeline for copy number alteration.
 

摘要翻译： 

多发性骨髓瘤（MM）及其前期状态MGUS以染色体畸变为特征。本研究基于500份MGUS与MM样本，全面解析了MM发展过程中复杂基因组事件的发生顺序。我们发现超二倍体MM（HMM）与非超二倍体MM（NHMM）是具有不同拷贝数变异进化路径的基因组学独立实体。在HMM中，9号、15号或19号染色体增益是最早出现的克隆性事件，甚至在MGUS阶段就已观察到这些克隆性变化。这些事件属于早期改变，可能是正常浆细胞向MGUS细胞初始转化的基础。然而，除15%的患者外，拷贝数异常可能不足以推动疾病进展为MM——在这部分患者中，我们仅在MM阶段观察到复杂的亚克隆缺失事件。在NHMM中，除驱动性易位外，13号染色体克隆性缺失和1q增益同样是在MGUS阶段就已观察到的早期事件。我们整合这些信息提出了拷贝数变异的发展时间线。

原文链接：

Deciphering the chronology of copy number alterations in Multiple Myeloma