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Selecting short length nucleic acids localized in exosomes improves plasma EGFR mutation detection in NSCLC patients

 Yoonjung Kim  ;  Saeam Shin  ;  Boyeon Kim  ;  Kyung-A Lee 
 Cancer Cell International, Vol.19 : 251, 2019 
Journal Title
 Cancer Cell International 
Issue Date
Circulating tumor DNA ; Epidermal growth factor receptor ; Extracellular vesicles ; Liquid biopsy ; Non-small cell lung cancer ; ddPCR
Background: Exosomal nucleic acid (exoNA) is a feasible target to improve the sensitivity of EGFR mutation testing in non-small cell lung cancer patients with limited cell-free DNA (cfDNA) mutant copies. However, the type and size of target exoNA related to the sensitivity of EGFR mutation testing has not been explored extensively. Methods: The type and size of target exoNA related to the sensitivity of EGFR mutation testing was evaluated using ddPCR. A total of 47 plasma samples was tested using short-length exoTNA (exosomal DNA and RNA) and cfDNA. Results: The sensitivity of short-length exoTNA (76.5%) was higher than that of cfDNA (64.7%) for detecting EGFR mutations in NSCLC patients. In EGFR-mutant NSCLC patients with intrathoracic disease (M0/M1a) or cases with low-copy T790M, the positive rate was 63.6% (N = 7/11) and 45.5% (N = 5/11) for short-length exoTNA and cfDNA, respectively. On average, the number absolute mutant copies of short-length exoTNA were 1.5 times higher than that of cfDNA. The mutant allele copies (Ex19del and T790M) in short-length exoTNA were relatively well preserved at 4 weeks after storage. The difference (%) in absolute mutant allele copies (Ex19del) between 0 days and 4 weeks after storage was - 61.0% for cfDNA. Conclusion: Target nucleic acids and their size distribution may be critical considerations for selecting an extraction method and a detection assay. A short-length exoTNA (200 bp) contained more detectable tumor-derived nucleic acids than exoDNA (~ 200 bp length or a full-length) or cfDNA. Therefore, a short-length exoTNA as a sensitive biomarker might be useful to detect EGFR mutants for NSCLC patients with low copy number of the mutation target.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
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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