MinimuMM-seq: Genome Sequencing of Circulating Tumor Cells for Minimally Invasive Molecular Characterization of Multiple Myeloma Pathology.
MinimuMM-seq: Genome Sequencing of Circulating Tumor Cells for Minimally Invasive Molecular Characterization of Multiple Myeloma Pathology.
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MinimuMM-seq：循环肿瘤细胞的基因组测序，用于多发性骨髓瘤病理学的微创分子表征。
DOI：
10.1158/2159-8290.cd-22-0482
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发表时间：
2023
期刊：
影响因子：
28.2
通讯作者：
Per
中科院分区：
文献类型：
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作者：
Dutta,AnkitK;Alberge,Jean-Baptiste;Lightbody,ElizabethD;Boehner,CodyJ;Dunford,Andrew;Sklavenitis-Pistofidis,Romanos;Mouhieddine,TarekH;Cowan,AnnieN;Su,NangKham;Horowitz,EricaM;Barr,Hadley;Hevenor,Laura;Beckwith,JennaB;Per
多发性骨髓瘤（MM）从明确定义的前体阶段发展而来;然而，侵入性骨髓（BM）活检限制了患者的筛查和监测策略。我们对261例患者（84例意义不明的单克隆丙种球蛋白病，155例郁积型多发性骨髓瘤和22例MM）的循环肿瘤细胞（CTC）进行了计数，84%的患者检出肿瘤细胞。我们开发了一种新的方法MinimuMM-seq，它可以通过高纯度CTC的全基因组测序来检测易位和拷贝数异常。在51例患者（24例为配对BM）的队列中应用于CTC能够检测100%的临床报告的BM活检事件，并且可以取代分子细胞遗传学用于诊断率和风险分类。在8名患者中的CTC的纵向采样揭示了可以在血液中追踪主要克隆，随着时间的推移，亚克隆具有克隆进化和移动动力学。我们的研究结果提供了概念证明，CTC检测和基因组分析可用于临床监测和管理MM疾病。SignificanceIn这项研究中，我们建立了一种方法，使CTC的计数和测序，以取代标准的分子细胞遗传学。CTC具有与BM浆细胞相同的特异性MM异常。连续CTC的纵向采样能够跟踪克隆动态随时间的变化，并检测高风险遗传亚克隆的出现。
Multiple myeloma (MM) develops from well-defined precursor stages; however, invasive bone marrow (BM) biopsy limits screening and monitoring strategies for patients. We enumerated circulating tumor cells (CTC) from 261 patients (84 monoclonal gammopathy of undetermined significance, 155 smoldering multiple myeloma, and 22 MM), with neoplastic cells detected in 84%. We developed a novel approach, MinimuMM-seq, which enables the detection of translocations and copy-number abnormalities through whole-genome sequencing of highly pure CTCs. Application to CTCs in a cohort of 51 patients, 24 with paired BM, was able to detect 100% of clinically reported BM biopsy events and could replace molecular cytogenetics for diagnostic yield and risk classification. Longitudinal sampling of CTCs in 8 patients revealed major clones could be tracked in the blood, with clonal evolution and shifting dynamics of subclones over time. Our findings provide proof of concept that CTC detection and genomic profiling could be used clinically for monitoring and managing disease in MM.SignificanceIn this study, we established an approach enabling the enumeration and sequencing of CTCs to replace standard molecular cytogenetics. CTCs harbored the same pathognomonic MM abnormalities as BM plasma cells. Longitudinal sampling of serial CTCs was able to track clonal dynamics over time and detect the emergence of high-risk genetic subclones.This article is highlighted in the In This Issue feature, p. 247