Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Departments of Medical Oncology, Pathology, and Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02214, USA.
Sci Transl Med. 2016 Nov 2;8(363):363ra147. doi: 10.1126/scitranslmed.aac7037.
Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring of MM genomic evolution on therapy by serial bone marrow biopsy is unfortunately impractical because it involves an invasive and painful procedure. We describe how noninvasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single-cell resolution recapitulate MM in the bone marrow. We demonstrate that CTCs provide the same genetic information as bone marrow MM cells and even reveal mutations with greater sensitivity than bone marrow biopsies in some cases. Single CTC RNA sequencing enables classification of MM and quantitative assessment of genes that are relevant for prognosis. We propose that the genomic characterization of CTCs should be included in clinical trials to follow the emergence of resistant subclones after MM therapy.
多发性骨髓瘤（MM）仍然是一种无法治愈的疾病，所有患者最终都会发展出治疗抵抗状态。MM 的克隆进化和遗传异质性是耐药疾病出现的可能解释。通过连续骨髓活检监测治疗过程中的 MM 基因组进化是不切实际的，因为它涉及到一种侵入性和痛苦的程序。我们描述了如何通过单细胞分辨率从外周血中无创和高度敏感地分离和鉴定循环肿瘤细胞（CTC），从而重现骨髓中的 MM。我们证明 CTC 提供了与骨髓 MM 细胞相同的遗传信息，在某些情况下甚至比骨髓活检更敏感地揭示突变。单个 CTC RNA 测序可实现 MM 的分类和对与预后相关基因的定量评估。我们建议在临床试验中包括 CTC 的基因组特征，以在 MM 治疗后跟踪耐药亚克隆的出现。
