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Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
Published on: August 24, 2017
Highly sensitive and noninvasive detection of epidermal growth factor receptor T790M mutation in non-small cell lung
Chen He1, Lixia Zheng, Yuzhong Xu
1Department of Respiratory, the Affiliated Shenzhen Bao'an Hospital of Southern Medical University, Shenzhen, Guangdong, 518101, China.
Background:
Epidermal growth factor receptor (EGFR) T790M mutation is associated with EGFR tyrosine kinase inhibitors resistance in non-small cell lung cancer (NSCLC). However, the tissue availability and technical feasibility limits the genotyping of EGFR T790M mutation in the clinical setting. The current study is, therefore, designed to develop a blood-based approach to detect the EGFR T790M mutation in advanced NSCLC patients.
Methods:
The detection of EGFR T790M mutation is based on the principle of mutant-enriched PCR. We assessed the basic performance efficiency of this method, and confirmed its clinical applicability. EGFR T790M mutation in the plasma samples obtained from 33 patients with gefitinib-resistant NSCLC was analyzed by the both mutant-enriched PCR and direct sequencing.
Results:
The sensitivity of this method for the detection of EGFR T790M mutation was as low as 0.1%. In the 33 subjects whose samples were analyzed, the mutant-enriched PCR indentified more EGFR T790M mutation than direct sequencing (36.4% vs. 6.1%, P=0.005), and the EGFR T790M mutation was more frequent in patients with EGFR activating mutations than those without EGFR activating mutations (62.5% vs. 11.8%, P=0.004). Patients with EGFR T790M mutation have a better prior efficacy of gefitinib compared to those without EGFR T790M mutation due to the occurrence of the EGFR activating mutations.
Conclusion:
The blood-based mutant-enriched PCR is an ideal noninvasive monitoring system for detecting EGFR T790M mutation for clinical application.
Insights
A new blood test accurately detects the Epidermal growth factor receptor (EGFR) T790M mutation in non-small cell lung cancer (NSCLC) patients. This noninvasive method overcomes tissue limitations for improved EGFR T790M mutation monitoring.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The T790M mutation in the Epidermal growth factor receptor (EGFR) confers resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC).
- Current methods for detecting EGFR T790M mutations face limitations due to tissue availability and technical challenges in clinical settings.
- There is a need for accessible methods to genotype EGFR T790M mutations in advanced NSCLC patients.
Purpose of the Study:
- To develop and validate a noninvasive, blood-based assay for detecting the EGFR T790M mutation in advanced NSCLC patients.
- To assess the clinical applicability and performance of a mutant-enriched PCR method for EGFR T790M mutation detection.
Main Methods:
- Utilized a mutant-enriched PCR technique for detecting EGFR T790M mutations in plasma samples.
- Assessed the sensitivity and basic performance of the mutant-enriched PCR method.
- Compared the results of mutant-enriched PCR with direct sequencing in 33 gefitinib-resistant NSCLC patients.
Main Results:
- The mutant-enriched PCR demonstrated high sensitivity, detecting EGFR T790M mutations down to 0.1%.
- Mutant-enriched PCR identified significantly more EGFR T790M mutations compared to direct sequencing (36.4% vs. 6.1%, P=0.005).
- EGFR T790M mutations were more prevalent in patients with prior EGFR activating mutations (62.5% vs. 11.8%, P=0.004) and associated with better gefitinib efficacy.
Conclusions:
- A blood-based mutant-enriched PCR assay is a highly effective noninvasive method for detecting EGFR T790M mutations.
- This approach offers an ideal solution for monitoring EGFR T790M mutations in clinical settings.
- The findings support the use of this blood-based test for improved management of NSCLC patients.
