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Updated: Jan 4, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Detection of rare and novel EGFR mutations in NSCLC patients: Implications for treatment-decision
A C Sousa1, C Silveira1, A Janeiro1
1GenoMed, Diagnósticos de Medicina Molecular, SA, Lisboa, Portugal.
Objectives:
Mutations in the gene that encodes epidermal growth factor receptor (EGFR) are biomarkers that predict how non-small cell lung cancer (NSCLC) patients respond to EGFR-targeted therapies collectively known as tyrosine kinase inhibitors (TKIs). Thus, EGFR genotyping provides crucial information for treatment decision. Both Sanger sequencing and real-time PCR methodologies are used for EGFR genotyping. However, methods based on real-time PCR have limitations, as they may not detect rare or novel mutations. The aim of this study was to determine the prevalence of rare mutations in the tyrosine kinase domain (exons 18-21) of the EGFR gene not targeted by the most frequently used real-time PCR approaches, i.e., the cobas® EGFR Mutation Test, and the Idylla™ EGFR Mutation Assay.
Methods:
A total of 1228 NSCLC patients were screened for mutations in exons 18-21 of the EGFR gene using Sanger sequencing.
Results:
We observed that 252 patients (∼20%) had at least one mutation in the EGFR gene, and 38 (∼3%) carried uncommon genetic alterations that would not be identified by the cobas® or the Idylla™ tests. We further found six new single mutations and seven previously unreported compound mutations. Clinical information and patient outcome are presented for these cases.
Conclusions:
This study highlights the value of sequencing-based approaches to identify rare mutations. Our results add to the inventory of known EGFR mutations, thus contributing to improved lung cancer precision treatment.
Insights
Sanger sequencing identified rare epidermal growth factor receptor (EGFR) mutations in 3% of non-small cell lung cancer (NSCLC) patients. These mutations, missed by common real-time PCR tests, are crucial for personalized lung cancer treatment.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR) mutations are key biomarkers for predicting non-small cell lung cancer (NSCLC) patient response to tyrosine kinase inhibitors (TKIs).
- EGFR genotyping is essential for guiding NSCLC treatment decisions.
- Current real-time PCR methods may fail to detect rare or novel EGFR mutations.
Purpose of the Study:
- To determine the prevalence of rare EGFR mutations in exons 18-21.
- To identify mutations not covered by standard cobas® and Idylla™ EGFR Mutation Assays.
Main Methods:
- Sanger sequencing was used to screen 1228 NSCLC patients for mutations in EGFR exons 18-21.
- Analysis focused on identifying rare and novel genetic alterations.
Main Results:
- Approximately 20% (252/1228) of patients had at least one EGFR mutation.
- 3% (38/1228) of patients harbored uncommon EGFR mutations undetectable by common real-time PCR assays.
- Six new single and seven new compound EGFR mutations were identified.
Conclusions:
- Sequencing-based methods are valuable for detecting rare EGFR mutations.
- The identified mutations expand the known landscape of EGFR alterations in NSCLC.
- Findings contribute to advancing precision medicine for lung cancer treatment.
