Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells
Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells
复制标题
通过脑脊液循环肿瘤细胞的新一代测序检测 NSCLC 软脑膜转移瘤中的驱动突变和耐药突变
DOI：
10.1158/1078-0432.ccr-17-0047
复制
发表时间：
2017-09-15
影响因子：
11.5
通讯作者：
Wu, Yi-Long
中科院分区：
文献类型：
--
作者：
Jiang, Ben-Yuan;Li, Yang-Si;Wu, Yi-Long
目的：脑膜转移在EGFR突变的非小细胞肺癌（NSCLC）中更常见。诊断是困难的，仅通过传统的成像，并导致对软脑膜metastasis.Experimental设计的耐药机制的认识不足：我们比较了CellSearch检测，薄层细胞学检查（TCT），和脑磁共振成像（MRI）在21例非小细胞肺癌患者怀疑软脑膜转移。包括416个癌症相关基因的下一代测序也进行了脑脊液循环肿瘤细胞（CSFCTC）的19 patients.Results：21例患者被诊断为软脑膜转移，和CSFCTC被捕获CellSearch在20例患者（中位数，969 CSFCTC/7.5 mL;范围，27- 14888）。CellSearch诊断软脑膜转移的敏感性为95.2%，高于TCT（12/21，57.1%）、MRI（10/21，47.6%）和MRI + TCT（19/21，90.5%）。仅在14例患者中的5例中发现CTC（中位数，2个CTC/7.5 mL;范围，2-4），这比CSFCTC低得多。CSFCTC的基因谱与原发肿瘤中鉴定的分子突变高度一致（17/19，89.5%）。在9例颅外病变患者中有7例检测到耐药基因EGFR T790 M，但在14例CSFCTC样本中仅1例检测到。结论：CellSearch捕获的CSFCTCs可能是诊断软脑膜转移的一种更敏感和有效的方法，并可作为NSCLC软脑膜转移患者基因谱的液体活检介质。(C)2017年AACR。
Purpose: Leptomeningeal metastases are more common in non-small cell lung cancer (NSCLC) with EGFR mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of leptomeningeal metastases.Experimental Design: We compared the CellSearch Assay, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected leptomeningeal metastases. Next-generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTC) of 19 patients.Results: Twenty-one patients were diagnosed with leptomeningeal metastases, and CSFCTCs were captured by CellSearch in 20 patients (median, 969 CSFCTCs/7.5 mL; range, 27-14,888). CellSearch had a sensitivity of 95.2% for leptomeningeal metas-tases diagnosis, which was higher than that of TCT (12/21, 57.1%), MRI (10/21, 47.6%), and MRI plus TCT (19/21, 90.5%), respectively. CTCs were found only in 5 of 14 patients (median, 2 CTCs/7.5 mL; range, 2-4), which was a much lower ratio than CSFCTCs. Genetic profiles of CSFCTCs were highly concordant with molecular mutations identified in the primary tumor (17/19, 89.5%). The resistance gene EGFR T790M was detected in 7 of 9 patients with extracranial lesions, but was detected in only 1 of 14 CSFCTC samples. Other potential resistant mutations, such as MET amplification and ERBB2 mutation, were also identified in CSFCTCs.Conclusions: CSFCTCs captured by CellSearch may be a more sensitive and effective way to diagnose leptomeningeal metastases, and may serve as a liquid biopsy medium for gene profiles in NSCLC patients with leptomeningeal metastases. (C) 2017 AACR.