Related Experiment Video
Updated: Mar 10, 2026
Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
Published on: August 24, 2017
Guide to detecting epidermal growth factor receptor (EGFR) mutations in ctDNA of patients with advanced
Nicola Normanno1, Marc G Denis2, Kenneth S Thress3
1Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione Giovanni Pascale", IRCCS, Napoli, Italy.
Abstract:
Cancer treatment is evolving towards therapies targeted at specific molecular abnormalities that drive tumor growth. Consequently, to determine which patients are eligible, accurate assessment of molecular aberrations within tumors is required. Obtaining sufficient tumor tissue for molecular testing can present challenges; therefore, circulating free tumor-derived DNA (ctDNA) found in blood plasma has been proposed as an alternative source of tumor DNA. The diagnostic utility of ctDNA for the detection of epidermal growth factor receptor (EGFR) mutations harbored in tumors of patients with advanced non-small-cell lung cancer (NSCLC) is supported by the results of several large studies/meta-analyses. However, recent real-world studies suggest that the performance of ctDNA testing varies between geographic regions/laboratories, demonstrating the need for standardized guidance. In this review, we outline recommendations for obtaining an accurate result using ctDNA, relating to pre-analytical plasma processing, ctDNA extraction, and appropriate EGFR mutation detection methods, based on clinical trial results. We conclude that there are several advantages associated with ctDNA, including the potential for repeated sampling - particularly following progression after first-line tyrosine kinase inhibitor (TKI) therapy, as TKIs targeting resistance mutations (eg T790M) are now approved for use in the USA/EU/Japan (at time of writing). However, evidence suggests that ctDNA does not allow detection of EGFR mutations in all patients with known mutation-positive NSCLC. Therefore, although tumor tissue should be the first sample choice for EGFR testing at diagnosis, ctDNA is a promising alternative diagnostic approach.
Insights
Liquid biopsies using circulating tumor DNA (ctDNA) show promise for detecting EGFR mutations in non-small cell lung cancer (NSCLC). While ctDNA offers advantages, tumor tissue remains the primary choice for initial EGFR testing.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Targeted cancer therapies require precise molecular profiling of tumors.
- Obtaining adequate tumor tissue for molecular testing can be challenging.
- Circulating tumor DNA (ctDNA) in blood plasma is an emerging alternative for tumor DNA analysis.
Purpose of the Study:
- To review recommendations for accurate ctDNA testing for EGFR mutations in advanced non-small cell lung cancer (NSCLC).
- To discuss the diagnostic utility and limitations of ctDNA compared to tumor tissue.
- To provide guidance on pre-analytical processing, ctDNA extraction, and mutation detection methods.
Main Methods:
- Review of clinical trial results and meta-analyses on ctDNA for EGFR mutation detection in NSCLC.
- Analysis of real-world data on ctDNA testing performance variations.
- Synthesis of recommendations for pre-analytical plasma processing, ctDNA extraction, and EGFR mutation detection.
Main Results:
- ctDNA testing shows diagnostic utility for EGFR mutations in advanced NSCLC, supported by large studies.
- Real-world data indicate variability in ctDNA test performance across regions and laboratories.
- ctDNA allows for repeated sampling, crucial for monitoring resistance mutations (e.g., T790M) after tyrosine kinase inhibitor (TKI) therapy.
Conclusions:
- ctDNA is a valuable tool for detecting EGFR mutations, especially when tumor tissue is insufficient or for post-treatment monitoring.
- Standardized guidance is needed to improve the consistency and accuracy of ctDNA testing.
- Tumor tissue remains the preferred sample for initial EGFR mutation testing at diagnosis, with ctDNA as a promising alternative.
More Related Videos
10:35A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction
Published on: April 5, 2018
05:17Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
