Clinical Application of Circulating Tumor Cells and Circulating Tumor DNA in Uveal Melanoma
Clinical Application of Circulating Tumor Cells and Circulating Tumor DNA in Uveal Melanoma
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DOI：
10.1200/po.17.00279
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发表时间：
2018-05-17
影响因子：
4.6
通讯作者：
Gray, Elfin S.
中科院分区：
文献类型：
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作者：
Beasley, Aaron;Isaacs, Timothy;Gray, Elfin S.
目的 评估使用循环肿瘤细胞 (CTC) 和循环肿瘤 DNA (ctDNA) 治疗葡萄膜黑色素瘤 (UM) 的可行性。患者和方法 使用低覆盖率全基因组测序来确定原发性 UM 肿瘤、ctDNA 和全基因组扩增的 CTC 中的体细胞染色体拷贝数改变 (SCNA)。使用与磁珠缀合的抗黑色素瘤相关硫酸软骨素抗体对 CTC 进行免疫捕获，并对 T 细胞 1 (MART1)/糖蛋白 100 (gp100)/S100 钙结合蛋白 β (S100 β) 识别的黑色素瘤抗原进行免疫染色。使用液滴数字聚合酶链式反应测定法对 GNAQ、GNA11、PLC beta 4 和 CYSLTR2 基因的突变进行定量。结果对从转移性 UM 患者分离的 CTC 和 ctDNA 进行 SCNA 分析，结果显示与去核原发肿瘤具有良好的一致性。在 30 名原发性 UM 患者的队列中，58% 的患者检测到 CTC（每 8 mL 血液 1 至 37 个 CTC），而只有 26% 的患者可检测到 ctDNA（1.6 至 29 拷贝/mL）。 CTC 或 ctDNA 的存在与肿瘤大小或其他预后标志物无关。然而，早期 UM 患者中 CTC 的频繁检测支持了一种模型，其中 CTC 可用于衍生与预后相关的肿瘤特异性 SCNA。原发肿瘤治疗后对 ctDNA 进行监测，比 F-18 标记的氟脱氧葡萄糖正电子发射断层扫描更早地检测到两名患者的转移性疾病。结论 局部 UM 中 CTC 的存在可用于确定预后 SCNA，而 ctDNA 可用于监测患者转移性疾病的早期迹象。这项研究为将 CTC 和 ctDNA 作为液体活检进行分析铺平了道路，这将有助于 UM 患者的治疗决策。 (C) 2018 年美国临床肿瘤学会
Purpose To evaluate the feasibility of using circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) for the management of uveal melanoma (UM).Patients and Methods Low-coverage whole-genome sequencing was used to determine somatic chromosomal copy number alterations (SCNAs) in primary UM tumors, ctDNA, and whole-genome amplified CTCs. CTCs were immunocaptured using an antimelanoma-associated chondroitin sulfate antibody conjugated to magnetic beads and immunostained for melanoma antigen recognised by T cells 1 (MART1)/glycoprotein 100 (gp100)/S100 calcium-binding protein beta (S100 beta). ctDNA was quantified using droplet digital polymerase chain reaction assay for mutations in the GNAQ, GNA11, PLC beta 4, and CYSLTR2 genes.Results SCNA analysis of CTCs and ctDNA isolated from a patient with metastatic UM showed good concordance with the enucleated primary tumor. In a cohort of 30 patients with primary UM, CTCs were detected in 58% of patients (one to 37 CTCs per 8 mL of blood), whereas only 26% of patients had detectable ctDNA (1.6 to 29 copies/mL). The presence of CTCs or ctDNA was not associated with tumor size or other prognostic markers. However, the frequent detection of CTCs in patients with early-stage UM supports a model in which CTCs can be used to derive tumor-specific SCNA relevant for prognosis. Monitoring of ctDNA after treatment of the primary tumor allowed detection of metastatic disease earlier than F-18-labeled fluorodeoxyglucose positron emission tomography in two patients.Conclusion The presence of CTCs in localized UM can be used to ascertain prognostic SCNA, whereas ctDNA can be used to monitor patients for early signs of metastatic disease. This study paves the way for the analysis of CTCs and ctDNA as a liquid biopsy that will assist with treatment decisions in patients with UM. (C) 2018 by American Society of Clinical Oncology