Mutation spectrum of EGFR in 21,324 patients with non-small cell lung cancer successfully tested by multiple platforms in a CAP-accredited laboratory.

Abstract

e13637 Background: Genotyping epidermal growth factor receptor ( EGFR) gene in patients with advanced non-small cell lung cancers (NSCLC) is essential to identify those patients who may benefit from targeted treatments. However, the testing methodology is still a puzzle for many clinicians. This study retrospectively reviewed the EGFR data from testing patients with NSCLC in our laboratory in 10 years. Methods: A total of 21,324 NSCLC cases successfully underwent EGFR genotyping in our laboratory for clinical therapeutic purpose, including 5,244 cases tested by Sanger sequencing, 13,329 cases tested by real-time PCR, and 2,751 tested by next generation sequencing-NGS. Results: 54.6%, 20% and 2.3% samples were recorded with tumor cell content (TCC) of < 40%, < 20% and 1% respectively. The average EGFR mutation rate was 45.1%, with 40.3% identified by Sanger sequencing, 46.5% by real-time PCR and 47.5% by NGS. Comparable EGFR mutation rates were observed in cases with 1%-20% TCC from real-time PCR and NGS platforms. In these cases with EGFR mutations, 93.3% of them carried a single EGFR mutation (92.1% with a classical mutation as 19del or L858R, and 7.9% with an uncommon mutation) and 6.7% harbored complex EGFR mutations. 65.3% of the cases carrying EGFR mutations identified by NGS also have tumor related variants in other genes. 26.5% more cases were found to have oncogenic driver mutations with therapeutic significance beyond EGFR by NGS. Conclusions: NGS may be the most optimal methodology to detect EGFR mutations in patients with NSCLC compared with Sanger sequencing and real-time PCR platforms from accuracy and comprehensiveness aspects, but some other issues, such as Turn Around Time (TAT), still should be considered in clinical practice.