Application of cerebrospinal fluid circulating cell-free DNA in the diagnosis and treatment of leptomeningeal metastases from non-small-cell lung cancer
10.3760/cma.j.issn.1009-9158.2019.12.010
- VernacularTitle: 脑脊液cfDNA在非小细胞肺癌脑膜转移诊疗中的应用
- Author:
Zhihui DONG
1
;
Kun CHEN
2
;
Yanchun MA
2
;
Ruofan HUANG
3
;
Ming GUAN
1
Author Information
1. Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
2. Department of Laboratory Medicine, Huashan Hospital North, Fudan University, Shanghai 201907, China
3. Department of Oncology, Huashan Hospital, Fudan University, Shanghai 200040, China
- Publication Type:Journal Article
- Keywords:
Carcinoma, non-small-cell lung;
Neoplasm metastasis;
Meningeal neoplasms;
Cell-free nucleic acids;
Cerebrospinal fluid;
High-throughput nucleotide sequencing
- From:
Chinese Journal of Laboratory Medicine
2019;42(12):1025-1030
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the application value of cerebrospinal fluid circulating cell-free DNA (cfDNA) in the diagnosis and treatment of leptomeningeal metastases in non-small-cell lung cancer (NSCLC).
Methods:Twenty-five patients with leptomeningeal metastases of NCSLC from Fudan University Huashan Hospital North during the period from September 2017 to November 2018 were enrolled. All 25 patients were confirmed leptomeningeal metastases by cerebrospinal fluid cytology and immunocytochemical staining of cytokeratin(CK7), carcinoembryonic antigen(CEA), thyroid transcription factor-1(TTF-1) and Ki67. The cerebrospinal fluid cfDNA was extracted and genetic variation of 12 genes including epidermal growth factor receptor(EGFR), TP53 and anaplastic lymphoma kinase(ALK) was detected by next-generation sequencing [PlasAim TM gene non-invasive detection of lung cancer (12 gene) kit, Singlera Genomics].The application value of cerebrospinal fluid cfDNA in the diagnosis and treatment of leptomeningeal metastases of NSCLC was analyzed with the cfDNA mutation data and the clinical follow-ups.
Results:Morphologically typical lung cancer tumor cells with tumor immunochemistry markerCK, CK7 and CEA were found in the cerebrospinal fluid of all 25 patients. Next generation sequencing of cerebrospinal fluid showed that 96% (24/25) patients had at least one single nucleotide variation (SNV) or copy number variation (CNV). The EGFR and TP53 mutations were identified in 80% (20/25) and 48%(12/25) of the patients, respectively. In addition, patients with bone metastases had a higher rate of EGFR mutations than those without bone metastases (100% vs 64%, P<0.05). Changes in the mutant allele frequency of EGFR and TP53 in cerebrospinal fluid were consistent with patients′ disease progression parameters including neurological symptoms, imaging, and tumor biomarkers. The results indicate that genetic alteration of EGFR in cerebrospinal fluid cfDNA is an actionable biomarker for targeted therapy of leptomeningeal metastases of lung cancer.
Conclusion:Cerebrospinal fluid cfDNA accurately reveals the unique genetic background of leptomeningeal metastasis in NSCLC, showing great application value in the diagnosis and treatment of the leptomeningeal metastasis of NSCLC.
