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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number251
JournalCancer Cell International
Volume19
Issue number1
DOIs
Publication statusPublished - 2019 Oct 1

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Exosomes
Nucleic Acids
Mutation
DNA
Alleles
Non-Small Cell Lung Carcinoma
Biomarkers
RNA

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

Cite this

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title = "Selecting short length nucleic acids localized in exosomes improves plasma EGFR mutation detection in NSCLC patients",
abstract = "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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Selecting short length nucleic acids localized in exosomes improves plasma EGFR mutation detection in NSCLC patients. / Kim, Yoonjung; Shin, Saeam; Kim, Boyeon; Lee, Kyung A.

In: Cancer Cell International, Vol. 19, No. 1, 251, 01.10.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Selecting short length nucleic acids localized in exosomes improves plasma EGFR mutation detection in NSCLC patients

AU - Kim, Yoonjung

AU - Shin, Saeam

AU - Kim, Boyeon

AU - Lee, Kyung A.

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Y1 - 2019/10/1

N2 - 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.

AB - 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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