BACKGROUND: Two types of epidermal growth factor receptor (EGFR) mutations in 
exon 19 and exon 21 (ex19del and L858R) are prevalent in lung cancer patients 
and sensitive to targeted EGFR inhibition. A resistance mutation in exon 20 
(T790M) has been found to accompany drug treatment when patients relapse. These 
three mutations are valuable companion diagnostic biomarkers for guiding 
personalized treatment. Quantitative polymerase chain reaction (qPCR)-based 
methods have been widely used in the clinic by physicians to guide treatment 
decisions. The aim of this study was to evaluate the technical and clinical 
sensitivity and specificity of the droplet digital polymerase chain reaction 
(ddPCR) method in detecting the three EGFR mutations in patients with lung 
cancer.
METHODS: Genomic DNA from H1975 and PC-9 cells, as well as 92 normal human blood 
specimens, was used to determine the technical sensitivity and specificity of 
the ddPCR assays. Genomic DNA of formalin-fixed, paraffin-embedded specimens 
from 78 Chinese patients with lung adenocarcinoma were assayed using both qPCR 
and ddPCR.
RESULTS: The three ddPCR assays had a limit of detection of 0.02% and a wide 
dynamic range from 1 to 20,000 copies measurement. The L858R and ex19del assays 
had a 0% background level in the technical and clinical settings. The T790M 
assay appeared to have a 0.03% technical background. The ddPCR assays were 
robust for correct determination of EGFR mutation status in patients, and the 
dynamic range appeared to be better than qPCR methods. The ddPCR assay for T790M 
could detect patient samples that the qPCR method failed to detect. About 49% of 
this patient cohort had EGFR mutations (L858R, 15.4%; ex19del, 29.5%; T790M, 
6.4%). Two patients with the ex19del mutation also had a naïve T790M mutation.
CONCLUSION: These data suggest that the ddPCR method could be useful in the 
personalized treatment of patients with lung cancer.