Epidermal growth factor receptor mutations in non–small cell lung cancer undetected by high-sensitivity allele-specific real-time polymerase chain reaction–based assays

Chia I. Shen, Hsiang Ling Ho, Yi Chen Yeh, Chao Hua Chiu, Teh Ying Chou

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)345-349
Number of pages5
JournalJournal of the Chinese Medical Association
Volume83
Issue number4
DOIs
Publication statusPublished - Apr 2020
Externally publishedYes

Keywords

  • Epidermal growth factor receptor mutation
  • Non–small cell lung cancer
  • Sequence analysis

ASJC Scopus subject areas

  • General Medicine

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