Epidermal growth factor receptor mutations in non–small cell lung cancer undetected by high-sensitivity allele-specific real-time polymerase chain reaction–based assays. Issue 4 (April 2020)

• Record Type: Journal Article
• Authors: Shen, Chia-I; Ho, Hsiang-Ling; Yeh, Yi-Chen; Chiu, Chao-Hua; Chou, Teh-Ying
• Is Part Of: Journal of the Chinese Medical Association. Volume 83:Issue 4(2020)
• Page Start: 345
• Page End: 349
• Publication Date: 2020-04
• Subjects: Epidermal growth factor receptor mutation -- Non–small cell lung cancer -- Sequence analysis; Medicine -- Periodicals; 610.5
• DOI: 10.1097/JCMA.0000000000000277
• Languages: English
• ISSNs: 1726-4901

Abstract

Abstract : Background: Identifying epidermal growth factor receptor (EGFR) mutation status is critical for planning lung cancer treatment. Sanger sequencing detects both known and novel mutations but shows poor sensitivity. High-sensitivity allele-specific real-time polymerase chain reaction (ASRP)-based assays offer quick and reliable results, but may overlook uncommon mutations. We aimed to define the rate at which high-sensitivity ASRP-based assays missed uncommon EGFR mutations. Methods: Non–small cell lung cancer specimens that were diagnosed as EGFR wild-type (EGFR-WT) by high-sensitivity ASRP-based assays and had residual DNA samples were sent for Sanger sequencing. Patient characteristics and clinical features were evaluated by chart review, and outcomes of EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy were studied. Results: Hundred DNA specimens diagnosed by high-sensitivity ASRP-based assays as EGFR-WT were rechecked by Sanger sequencing. Two samples which were re-biopsy specimens from patients with EGFR mutations were excluded from the analysis. Sanger sequencing was failed in 24 samples. Among the remaining 74 samples, 6 (8.1%) had EGFR mutations—one exhibited exon 19 deletion (delT751_I759insS), two exhibited substitution mutations (S768I+V769L and L861Q), and three exhibited exon 20 insertions (N771_P772insN, P772_H773insHP, and H773_V774insAH). Only the patient with the exon 19 deletion had received EGFR-TKI therapy. Although the best tumor response was only stable disease, this was maintained for >10 months. Conclusion: High-sensitivity ASRP-based assays can overlook uncommon mutations. This detection failure rate is worth noting, especially when treating patients from regions known to have a high prevalence of EGFR mutation. Patients carrying uncommon mutations may still benefit from EGFR-TKI therapy.