Frequency and significance of epidermal growth factor receptor mutations detected by PCR methods in patients with non-small cell lung cancer

Epidermal growth factor receptor (EGFR) is the most important driver gene of non-small cell lung cancer (NSCLC) as EGFR mutations determine the efficacy of EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. In the present study, the comprehensive ability of widely used polymerase chain reaction (PCR) methods to detect EGFR mutations was determined. Among the 35 EGFR mutations detected via the direct sequencing of 73 patients with NSCLC, 11 types were identified in exons 18, 19 and 21. Among the 11 mutation types, all exon 18 and 21 mutations were identified by 2 widely used PCR methods, namely, Scorpion-Amplification Refractory Mutation System and cobas v2. However, among the 9 different exon 19 deletions, 3 types were not identified by the 2 methods. In addition, 25 samples with EGFR mutations were analyzed by the 2 methods, including a sample from a patient with an unidentified exon 19 deletion, the T751_I759 deletion and insertion S; this patient had long-term disease control as a result of EGFR-TKI therapy. The 2 methods could not detect this unidentified deletion, whereas sizing capillary electrophoresis for the comprehensive detection of exon 19 deletions detected this deletion. It is generally thought that patients with exon 19 mutations have higher response rates to EGFR-TKI therapy than patients with exon 21 mutations. The present study confirmed the EGFR mutation status by comparing the mutations with the Catalog Of Somatic Mutations In Cancer, which is the world's largest and most comprehensive resource for analyzing the effects of somatic mutations in human cancers. The predicted frequency of EGFR mutations identified by the 2 methods was 85%. The frequency of mutations detectable by the 2 methods was less for exon 19 than exon 21. Therefore, the results of the present study suggest that decreasing false-negative detection of exon 19 deletions is crucial for the clinical testing of EGFR mutations.