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Oncotarget. 2017 Jan 24;8(4):5861-5873. doi: 10.18632/oncotarget.14390.

Total DNA input is a crucial determinant of the sensitivity of plasma cell-free DNA EGFR mutation detection using droplet digital PCR.

Author information

1
Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Abstract

We evaluated the use of droplet digital PCR (ddPCR) to detect plasma cell-free DNA (cfDNA) epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung cancer (NSCLC) patients. Compared with tumor-tissue-based detection, the sensitivity of ddPCR for detecting plasma cfDNA tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutations was 61.3%, the specificity was 96.7%, and the consistency rate was 81.4% (κ=0.605, 95% confidence interval: 0.501-0.706, p <0.0001). The sensitivity declined from 82.6% to 46.7% with decreasing cfDNA inputs (p=0.028). The plasma cfDNA concentration correlated with gender (males vs.females =11.69 ng/mL vs. 9.508 ng/mL; p=0.044), EGFR mutation status (tumor-tissue EGFR mutation-positive (EGFR M+) vs. EGFR mutation-negative (EGFR M-) = 9.61 ng/mL vs. 12.82 ng/mL; p =0.049) and specimen collection time (≤2 years vs. >2 years=13.83 ng/mL vs. 6.575 ng/mL; p <0.001), and was greater in tumor-tissue EGFR M+ / plasma EGFR M+ patients than in tumor-tissue EGFR M+/plasma EGFR M- patients (11.61 vs. 7.73 ng/mL, respectively; p=0.003). Thus total cfDNA input crucially influences the sensitivity of plasma cfDNA EGFR mutation testing with ddPCR. Such analysis could be an effective supplemental test for advanced NSCLC patients.

KEYWORDS:

DNA concentration; advanced non-small cell lung cancer; droplet digital PCR; epidermal growth factor receptor; plasma cell-free DNA

PMID:
28052016
PMCID:
PMC5351596
DOI:
10.18632/oncotarget.14390
[Indexed for MEDLINE]
Free PMC Article

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