Abstract
BackgroundThe 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.MethodsWe 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.ResultsAll 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.ConclusionThese 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.
Highlights
The exosomal nucleic acid 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 epider‐ mal growth factor receptor (EGFR) inhibitor therapy
The low abundance of Circulating tumor DNA (ctDNA) is an obstacle for detecting EGFR mutations in NSCLC patients with acquired tyrosine kinase inhibitors (TKIs)-resistance
We demonstrated the optimal analytical method to improve the sensitivity of detecting EGFR mutations in different types of clinical samples
Summary
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 epider‐ mal growth factor receptor (EGFR) inhibitor therapy. Kim et al Cancer Cell Int (2021) 21:50 surveillance of clonal evolution, including acquired resistance alterations following TKI therapy, is essential for precision medicine. This frequent surveillance cannot be effectively achieved using tissue biopsy specimens, due to the possibility of inappropriate or inadequate sampling that misses portions of the tumor that are developing treatment resistance or have acquired new driver mutations due to tumor heterogeneity [6]. The pre-analytical steps for maximizing the tumor-derived nucleic acid concentration and ultra-sensitive analytical techniques were essentially required to achieve the optimal sensitivity of the EGFR mutation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
