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Exosome-based detection of EGFR T790M in plasma and pleural fluid of prospectively enrolled non-small cell lung cancer patients after first-line tyrosine kinase inhibitor therapy

 Yoonjung Kim  ;  Saeam Shin  ;  Kyung-A Lee 
 CANCER CELL INTERNATIONAL, Vol.21(1) : 50, 2021-01 
Journal Title
Issue Date
Circulating tumor DNA ; Epidermal growth factor receptor ; Extracellular vesicles ; Liquid biopsy ; Non-small cell lung cancer ; Tyrosine kinase inhibitors
Background: The exosomal nucleic acid (exoNA) from the plasma and pleural fluid can potentially provide means to identify genomic changes in non-small cell lung cancer (NSCLC) patients who develop resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy. Methods: We compared the performance of the following tools to detect EGFR mutations in 54 plasma samples and 13 pleural fluid using cfDNA, combined TNA (exoTNA + cfTNA), or total cellular DNA: droplet digital PCR (ddPCR), the Cobas® EGFR Mutation Test v2 (Cobas) and NGS with Oncomine Pan-Cancer Cell-Free Assay. Results: All three of these platforms demonstrated 100% specificity in the detection of EGFR mutations in the plasma. In the detection of an activating mutation (exon 19 deletion and L858R), Cobas using cfDNA, ddPCR using combined TNA, and NGS using combined TNA showed a sensitivity of 93, 95.3, and 93.8%, respectively. For T790M mutation detection, the Cobas, ddPCR, and NGS showed a sensitivity of 64.7, 88.2, and 93.3%, respectively. Pleural fluid analysis revealed enrichment of the T790M mutant copies in the exosomes. ddPCR using exoTNA showed higher sensitivity than did total cellular DNA from the pleural fluid. Conclusion: These results demonstrated that combined TNA in the plasma and exoTNA in the pleural fluid can be used to evaluate low-abundant EGFR mutant copies in NSCLC.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yoon Jung(김윤정) ORCID logo https://orcid.org/0000-0002-4370-4265
Shin, Saeam(신새암) ORCID logo https://orcid.org/0000-0003-1501-3923
Lee, Kyung A(이경아) ORCID logo https://orcid.org/0000-0001-5320-6705
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