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Updated: Nov 14, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Detection of MET Exon 14 Skipping Alterations in Lung Cancer Clinical Samples Using a PCR-Based Approach
Jane S Y Sui1,2, Stephen P Finn1,3,4, Steven G Gray5,6,7
1Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St. James's Hospital, Dublin, Ireland.
Abstract:
The receptor tyrosine kinase (RTK) c-MET plays important roles in cancer, yet despite being frequently overexpressed, clinical responses to targeting this receptor have been limited in the clinical setting. A singular significant challenge has been the accurate identification of biomarkers for the selection of responsive patients. However, recently mutations which result in the loss of exon 14 (called METex14 skipping) have emerged as novel biomarkers in non-small cell lung carcinomas (NSCLC) to predict for responsiveness to targeted therapy with c-MET inhibitors. Currently, the diverse genomic alterations responsible for METex14 skipping pose a challenge for routine clinical diagnostic testing. Next generation sequencing (NGS) is the current gold standard for identifying the diverse mutations associated with METex14, but the cost for such a procedure remains to some degree prohibitive as often NGS is requested on a case-by-case basis, and many hospitals may not even have the capacity or resources to conduct NGS.However, PCR-based approaches to detect METex14 have been developed which can be conducted in most routine hospital laboratories and may therefore allow a cost-effective approach to pre-screen patients that may respond to c-MET inhibitors prior to conducting NGS, or until all patients will have NGS conducted as routine practise. In this chapter, we describe one such PCR-based approach for screening samples for the detection of METex14 in NSCLC.
Insights
METex14 skipping mutations are key biomarkers for non-small cell lung cancer (NSCLC) patients who may benefit from c-MET inhibitors. A new PCR-based method offers a cost-effective way to detect these mutations, improving patient selection for targeted therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The c-MET receptor tyrosine kinase (RTK) is crucial in cancer, but clinical responses to its inhibitors are often limited.
- Accurate biomarker identification is essential for selecting patients likely to respond to c-MET targeted therapy.
- METex14 skipping mutations in non-small cell lung carcinomas (NSCLC) are emerging as predictive biomarkers for c-MET inhibitor responsiveness.
Purpose of the Study:
- To address the diagnostic challenges posed by diverse genomic alterations causing METex14 skipping.
- To present a cost-effective, accessible method for detecting METex14 skipping mutations in NSCLC.
- To facilitate pre-screening of patients for c-MET inhibitor therapy.
Main Methods:
- Development and description of a Polymerase Chain Reaction (PCR)-based approach for detecting METex14 skipping.
- Utilizing standard hospital laboratory capabilities for mutation screening.
- Comparison with Next-Generation Sequencing (NGS) as the current gold standard.
Main Results:
- PCR-based detection offers a viable alternative to NGS for identifying METex14 skipping.
- This approach can be implemented in routine hospital laboratories, enhancing accessibility.
- Enables cost-effective pre-screening of NSCLC patients for targeted therapy.
Conclusions:
- PCR-based screening for METex14 skipping mutations provides a practical and economical solution for NSCLC patient stratification.
- This method can improve the selection of patients for c-MET inhibitor treatment, potentially overcoming NGS limitations.
- Facilitates wider application of precision medicine in NSCLC management.
