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Updated: Jan 21, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Deep targeted sequencing analysis of hot spot mutations in non-small cell lung cancer patients from the Middle
Pierre Khoueiry1, Ghina Fakhri2, Reem Akel2
1Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.
Background:
The overall 5-year survival of lung cancer remains dismal despite the current treatment regimens. Testing for driver mutations has become routine practice for oncologists due to the presence of targeted therapy readily available for patients. Deep targeted sequencing through next generation sequencing (NGS) is an adequate methodology to detect mutations at multi-genetic levels. The molecular pathology of non-small cell lung cancer (NSCLC) is poorly understood in the Middle East and, to date, no other reports have been published on deep targeted sequencing of lung adenocarcinoma (LUAD) tissues.
Methods:
Deep targeted sequencing using TruSeq Amplicon Cancer panel of 48 genes was performed on 85 formalin-fixed paraffin-embedded tissues from patients with LUAD who were treatment-naive at the time of the collection. Variants with an allele frequency higher than 10% were retained.
Results:
Variant calling identified a total of 2,455 variants of which missense mutations were the most frequent (75.6%). All of our samples showed at least one mutation in one of the 10 most commonly mutated genes with FLT3 being the gene with the highest mutation rate (67%). TP53, KRAS and STK11 were the second, third and fourth most commonly mutated genes, respectively while EGFR mutation rate reached 22.4%.
Conclusions:
To the best of our knowledge, this is the first hot spot profiling study on patients from this area. The frequencies of mutated genes presented in our study showed similarity to other reported outcomes. At least one mutation was detected in our cohort of LUAD.
Insights
This study analyzed lung adenocarcinoma (LUAD) mutations in the Middle East using deep targeted sequencing. Most patients had at least one mutation, with FLT3, TP53, KRAS, and STK11 being frequently altered, providing crucial molecular insights.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer survival rates remain low despite current treatments.
- Targeted therapies necessitate routine driver mutation testing.
- Next-generation sequencing (NGS) enables deep targeted sequencing for multi-genetic mutation detection.
- The molecular landscape of non-small cell lung cancer (NSCLC) in the Middle East is understudied, with no prior deep targeted sequencing reports on lung adenocarcinoma (LUAD) tissues.
Purpose of the Study:
- To perform deep targeted sequencing on LUAD tissues from the Middle East.
- To identify common mutations in LUAD patients in this region.
- To contribute to understanding the molecular pathology of LUAD.
Main Methods:
- Deep targeted sequencing was conducted on 85 treatment-naive LUAD formalin-fixed paraffin-embedded tissues.
- The TruSeq Amplicon Cancer panel, covering 48 genes, was utilized.
- Variants with an allele frequency >10% were selected for analysis.
Main Results:
- A total of 2,455 variants were identified, with missense mutations being the most common (75.6%).
- All samples harbored at least one mutation in the top 10 most frequently mutated genes.
- FLT3 showed the highest mutation rate (67%), followed by TP53, KRAS, and STK11. EGFR mutations were found in 22.4% of cases.
Conclusions:
- This represents the first hotspot profiling study of LUAD patients from the Middle East.
- Observed mutation frequencies align with previously reported outcomes.
- The study confirmed the presence of at least one mutation in the investigated LUAD cohort.
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