文章：

多发性骨髓瘤中获得性高风险染色体不稳定表型：跳跃性1q综合征

An acquired high-risk chromosome instability phenotype in multiple myeloma: Jumping 1q Syndrome

原文发布日期：2019-08-09

DOI: 10.1038/s41408-019-0226-4

类型: Article

开放获取: 是

英文摘要：

Patients with multiple myeloma (MM) accumulate adverse copy number aberrations (CNAs), gains of 1q21, and 17p deletions during disease progression. A subset of these patients develops heightened 1q12 pericentromeric instability and jumping translocations of 1q12 (JT1q12), evidenced by increased copy CNAs of 1q21 and losses in receptor chromosomes (RC). To understand the progression of these aberrations we analyzed metaphase cells of 50 patients with ≥4 CNAs of 1q21 by G-banding, locus specific FISH, and spectral karyotyping. In eight patients with ≥5 CNAs of 1q21 we identified a chromosome instability phenotype similar to that found in ICF syndrome (immunodeficiency, centromeric instability, and facial anomalies). Strikingly, the acquired instability phenotype identified in these patients demonstrates the same transient structural aberrations of 1q12 as those found in ICF syndrome, suggesting similar underlying pathological mechanisms. Four types of clonal aberrations characterize this phenotype including JT1q12s, RC deletions, 1q12-21 breakage-fusion-bridge cycle amplifications, and RC insertions. In addition, recurring transient aberrations include 1q12 decondensation and breakage, triradials, and 1q micronuclei. The acquired self-propagating mobile property of 1q12 satellite DNA drives the continuous regeneration of 1q12 duplication/deletion events. For patients demonstrating this instability phenotype, we propose the term “Jumping 1q Syndrome.”
 

摘要翻译： 

多发性骨髓瘤（MM）患者在疾病进展过程中会积累不利的拷贝数畸变（CNAs），包括1q21区段扩增和17p缺失。部分患者出现显著的1q12着丝粒周围不稳定性及1q12跳跃易位（JT1q12），表现为1q21拷贝数畸变增加和受体染色体（RC）缺失。为解析这些畸变的进展机制，我们通过G显带、位点特异性FISH及光谱核型分析技术，对50例携带≥4个1q21拷贝数畸变患者的中期细胞进行了研究。在8例携带≥5个1q21拷贝数畸变的患者中，我们发现了与ICF综合征（免疫缺陷、着丝粒不稳定及面部异常）相似的染色体不稳定性表型。值得注意的是，这些患者获得性不稳定性表型呈现出的1q12短暂性结构畸变与ICF综合征中的表现一致，提示二者存在相似的潜在病理机制。该表型具有四种克隆性畸变特征：1q12跳跃易位、受体染色体缺失、1q12-21断裂-融合-桥循环扩增及受体染色体插入。此外，反复出现的短暂性畸变包括1q12解凝聚与断裂、三射体及1q微核。获得性1q12卫星DNA自我增殖的移动特性驱动着1q12重复/缺失事件的持续再生。针对呈现该不稳定性表型的患者，我们建议采用“跳跃性1q综合征”这一命名。

原文链接：

An acquired high-risk chromosome instability phenotype in multiple myeloma: Jumping 1q Syndrome