Use of capture-based next-generation sequencing to detect ALK fusion in plasma cell-free DNA of patients with non-small-cell lung cancer

• Published in: Oncotarget Vol. 8; no. 2; pp. 2771 - 2780
• Main Authors: Cui, Shaohua, Zhang, Wei, Xiong, Liwen, Pan, Feng, Niu, Yanjie, Chu, Tianqing, Wang, Huimin, Zhao, Yizhuo, Jiang, Liyan
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 10.01.2017
• Subjects: Adult; Aged; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Cell-Free Nucleic Acids; Computational Biology - methods; DNA, Neoplasm; Female; High-Throughput Nucleotide Sequencing; Humans; Kaplan-Meier Estimate; Liquid Biopsy - methods; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Middle Aged; Neoplasm Staging; Oncogene Proteins, Fusion - genetics; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - therapeutic use; Pyridines - therapeutic use; Receptor Protein-Tyrosine Kinases - genetics; Reproducibility of Results; Research Paper; Sensitivity and Specificity; Treatment Outcome; cell-free DNA (cfDNA); capture-based next-generation sequencing; non-small-cell lung cancer (NSCLC); liquid biopsy; anaplastic lymphoma kinase (ALK)
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.13741

Capture-based next-generation sequencing (NGS) is a potentially useful diagnostic method to measure tumor tissue DNA in blood as it can identify concordant mutations between cell-free DNA (cfDNA) and primary tumor DNA in lung cancer patients. In this study, the sensitivity, specificity and accuracy of capture-based NGS for detecting ALK fusion in plasma cfDNA was assessed. 24 patients with tissue ALK-positivity and 15 who did not harbor ALK fusion were enrolled. 13 ALK-positive samples were identified by capture-based NGS among the 24 samples with tissue ALK-positivity. In addition to EML4-ALK, 2 rare fusion types (FAM179A-ALK and COL25A1-ALK) were also identified. The overall sensitivity, specificity and accuracy for all cases were 54.2%, 100% and 71.8%, respectively. For patients without distant metastasis (M0-M1a) and patients with distant metastasis (M1b), the sensitivities were 28.6% and 64.7%, respectively. In the 15 patients who received crizotinib, the estimated median PFS was 9.93 months. Thus, captured-based NGS has acceptable sensitivity and excellent specificity for the detection of ALK fusion in plasma cfDNA, especially for patients with distant metastasis. This non-invasive method is clinically feasible for detecting ALK fusion in patients with advanced-stage NSCLC who cannot undergo traumatic examinations or have insufficient tissue samples for molecular tests.