Related Experiment Video
Updated: Oct 19, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Optimising fusion detection through sequential DNA and RNA molecular profiling of non-small cell lung cancer
David A Moore1, Sarah Benafif2, Benjamin Poskitt3
1CRUK Lung Cancer Centre of Excellence, UCL Cancer Institute, UCL, London, United Kingdom; Department of Cellular Pathology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
Objectives:
There is an increasing number of driver fusions in NSCLC which are amenable to targeted therapy. Panel testing for fusions is increasingly appropriate but can be costly and requires adequate good quality biopsy material. In light of the typical mutual exclusivity of driver events in NSCLC, the objective of this study was to trial a novel testing pathway, supported by industrial collaboration, in which only patients negative for driver mutations on DNA-NGS were submitted for fusion panel analysis.
Materials And Methods:
Over 18 months, all patients from a single centre with non-squamous NSCLC were submitted for DNA-NGS, plus ALK and ROS1 immunohistochemistry +/- FISH. Those which were negative for a driver mutation were then recalled for RNA panel testing.
Results:
307 samples were referred for DNA-NGS mutation analysis, of which, 10% of cases were unsuitable for or failed DNA-NGS analysis. Driver mutations were detected in 61% (167/275) of all those successfully tested. Of those without a driver mutation and with some remaining tissue available, 28% had insufficient tissue/extracted RNA or failed RNA-NGS. Of those successfully tested, 24% (17/72) had a fusion gene detected involving either ALK, ROS, MET, RET, FGFR or EGFR. Overall, 66% (184/277) of patients had a driver event detected through the combination of DNA and RNA panels.
Conclusion:
Sequential DNA and RNA based molecular profiling increased the efficacy of detecting fusion driven NSCLCs. Continued optimisation of tissue procurement, handling and the diagnostic pathways for gene fusion analysis is necessary to reduce analysis failure rates and improve detection rate for treatment with the next generation of small molecule inhibitors.
Insights
A new sequential testing approach for non-small cell lung cancer (NSCLC) improves detection of actionable driver fusions. This method prioritizes patients negative for driver mutations on DNA next-generation sequencing (NGS) for RNA panel testing, enhancing targeted therapy identification.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Non-small cell lung cancer (NSCLC) management increasingly relies on targeted therapies for driver fusions.
- Current fusion panel testing is costly and requires ample, high-quality biopsy material.
- Driver events in NSCLC are typically mutually exclusive, allowing for sequential testing strategies.
Purpose of the Study:
- To evaluate a novel, cost-effective molecular testing pathway for NSCLC.
- To identify patients with actionable driver fusions by prioritizing those negative for driver mutations via DNA-NGS.
- To improve the detection rate of fusion-driven NSCLC amenable to targeted therapy.
Main Methods:
- A sequential diagnostic pathway was implemented over 18 months for non-squamous NSCLC patients.
- Initial testing involved DNA-NGS and ALK/ROS1 immunohistochemistry +/- FISH.
- Patients negative for driver mutations were recalled for RNA panel testing if sufficient tissue remained.
Main Results:
- 61% of successfully DNA-NGS tested samples harbored driver mutations.
- Among samples negative for driver mutations, 24% (17/72) had detectable fusions (ALK, ROS, MET, RET, FGFR, EGFR).
- The combined DNA and RNA panel approach detected a driver event in 66% of patients.
Conclusions:
- Sequential DNA and RNA-based molecular profiling enhances the detection of fusion-driven NSCLC.
- Optimizing tissue handling and diagnostic pathways is crucial to reduce failure rates in gene fusion analysis.
- Improved detection rates facilitate treatment with next-generation small molecule inhibitors.
More Related Videos
09:49Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
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
