Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy
Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy
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DOI：
10.1093/annonc/mdy009
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发表时间：
2018-04-01
影响因子：
50.5
通讯作者：
Wu, Y. L.
中科院分区：
文献类型：
--
作者：
Li, Y. S.;Jiang, B. Y.;Wu, Y. L.
背景资料：脑膜转移（LM）在表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）中更常见。由于有限的访问软脑膜病变，本研究的目的是探讨潜在的作用，脑脊液（CSF）作为液体活检的LM患者的来源。患者和方法：原发性肿瘤，CSF和血浆在非小细胞肺癌与LM进行了测试，通过下一代测序。总共有45例疑似LM的患者接受了腰椎穿刺，并与EGFR突变诊断为LM的患者入组。结果：共有28例患者入组该队列; CSF和血浆可在26例患者，分别。分别在100%（26/26）、84.6%（22/26）和73.1%（19/26）的包含CSF无细胞DNA（cfDNA）、CSF沉淀物和血浆的样品中检测到驱动基因; 92.3%（24/26）的患者在CSF cfDNA中具有比其他两种培养基高得多的等位基因分数。与血浆和原代组织中的那些相比，在CSF cfDNA中捕获独特的遗传谱。多拷贝数变异（CNV）主要在CSF cfDNA中发现，在47.8%（11/23）的患者中发现的MET拷贝数增加是最常见的，而其他CNV包括ERBB 2、KRAS、ALK和MYC。此外，在CSF cfDNA中TP 53的杂合性丢失率（洛）为73.1%（19/26），明显高于血浆（2/26，7.7%; P
Background: Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.Results: A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P