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Updated: Feb 19, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Tumor molecular profiling of NSCLC patients using next generation sequencing
Nikolaos Tsoulos1, Eirini Papadopoulou1, Vasiliki Metaxa-Mariatou1
1GeneKor Medical S.A., Athens 15344, Greece.
Abstract:
Non‑small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues. Furthermore, the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel was used for fusion RNA transcript analysis. The mutation spectrum of the tumors was determined in a cohort of 502 patients with NSCLC using the aforementioned targeted gene panels. The panel used for tumor DNA analysis in this study exhibited high rates (100%) of sensitivity, specificity and reproducibility at a mutation allelic frequency of 3%. At least one DNA mutation was detected in 374 patients (74.5%) and an RNA fusion was identified in 16 patients, (3.2%). In total, alterations in a cancer-driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested. Among the NSCLC patients, 23% presented a mutation in a gene associated with approved or emerging targeted therapy. More specifically, 13.5% (68/502) presented a mutation in a gene with approved targeted therapy (EGFR, ALK, ROS1) and 9.4% (47/502) had an alteration in a gene related to emerging targeted therapies (ERBB2, BRAF, MET and RET). Furthermore, 51.6% of the patients had a mutation in a gene that could be related to an off label therapy or indicative for access to a clinical trial. Thus, the targeted NGS panel used in this study is a reliable approach for tumor molecular profiling and can be applied in personalized treatment decision making for NSCLC patients.
Insights
Next-generation sequencing (NGS) accurately profiles non-small cell lung cancer (NSCLC) tumors. Targeted gene panels identify actionable mutations, aiding personalized treatment decisions for NSCLC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Non-small cell lung cancer (NSCLC) is the most common lung cancer subtype.
- Targeted therapies are crucial for NSCLC management, necessitating precise molecular profiling.
- Next-generation sequencing (NGS) is a key technology for tumor characterization.
Purpose of the Study:
- To evaluate the performance of custom targeted gene panels for NSCLC molecular profiling.
- To determine the mutation spectrum in a cohort of 502 NSCLC patients.
- To assess the utility of NGS in identifying actionable mutations for personalized treatment.
Main Methods:
- Utilized a custom 23-gene multiplex amplification hotspot panel for DNA analysis from FFPE tissues.
- Employed the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel for RNA fusion transcript analysis.
- Analyzed tumor DNA and RNA from 502 NSCLC patients.
Main Results:
- The DNA panel demonstrated 100% sensitivity, specificity, and reproducibility at 3% allelic frequency.
- DNA mutations were found in 74.5% of patients, and RNA fusions in 3.2%.
- Alterations in cancer-driver genes were identified in 77.6% of tumors, with 23% having mutations actionable by targeted or emerging therapies.
Conclusions:
- Targeted NGS panels are reliable tools for comprehensive tumor molecular profiling in NSCLC.
- This approach facilitates personalized treatment decision-making by identifying targetable genetic alterations.
- The study highlights the high prevalence of actionable mutations in NSCLC, underscoring the importance of molecular characterization.
