文章：

意义未明的单克隆丙种球蛋白病、冒烟型及症状性多发性骨髓瘤的细胞遗传学特征：基于1087例高纯度浆细胞的研究

Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells

原文发布日期：2 December 2023

DOI: 10.3390/cancers15235690

类型: Article

开放获取: 是

英文摘要：

The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p),MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases.IGH::CCND1was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) andMYC-R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort.

摘要翻译： 

本研究旨在探究不同疾病阶段浆细胞肿瘤（PCNs）的细胞遗传学特征，共纳入1087例患者，包括意义未明的单克隆丙种球蛋白病（MGUS）、冒烟型多发性骨髓瘤（SMM）、新诊断多发性骨髓瘤（NDMM）以及难治/复发多发性骨髓瘤（RRMM）。通过对高纯度浆细胞样本进行荧光原位杂交（FISH）分析，发现96%的患者至少存在一种细胞遗传学异常。基因组复杂性从MGUS到SMM，再到NDMM和RRMM逐步增加，主要由1q增益、del(17p)、MYC重排（MYC-R）、del(1p)及四倍体驱动。在RRMM病例中，高危细胞遗传学异常（59%）、1q增益（44%）和del(17p）（23%）的发生率显著升高，且亚克隆存在比例较高（48%）。IGH::CCND1重排在26%的病例中被检出，在不同种族、年龄或疾病组间未见明显差异。同步染色体核型分析与FISH结果显示，异常核型发生率与肿瘤性浆细胞浸润程度、基因组复杂性以及特定异常（如del(17p）和MYC-R）的存在密切相关。约98%的异常核型病例呈现复杂核型，其中多数具有五种及以上异常。1号染色体结构异常最为常见，见于65%的病例。亚克隆与复合核型的频繁出现凸显了该队列中基因组的异质性与不稳定性。

原文链接：

Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells