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Updated: Jun 12, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Clinical Utility of Circulating Tumor DNA for Detecting Lung Cancer Mutations by Targeted Next-Generation Sequencing
Yi Sun1, Xu Zhang2, Xinhua Yang2
1Pediatric, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Background:
Circulating tumor deoxyribonucleic acid (ctDNA) is increasingly applied in clinical practice. This study aimed to explore clinical utility of a minimal invasive and sensitive way of ctDNA for next-generation sequencing in non-small cell lung cancer (NSCLC) with inadequate tumor samples.
Methods:
Targeted DNA sequencing was performed on tissue biopsies and matched plasma samples from 60 patients with NSCLC.
Results:
A total of 13 driving genes were detected in 60 matched tissue DNA (tDNA) and ctDNA samples. Overall concordance rate was 75.47%, with 77.55% sensitivity and 50% specificity. Epidermal growth factor receptor (EGFR) mutations were the most common in both tDNA and ctDNA samples. Among other mutated genes were tumor protein p53 (TP53), erb-b2 receptor tyrosine kinase 2 (ERBB2), anaplastic lymphoma kinase (ALK), cyclin-dependent kinase inhibitor 2A (CDKN2A), ros proto-oncogene 1, and receptor tyrosine kinase (ROS1). Mutations in b-raf proto-oncogene, serine/threonine kinase (BRAF), cluster of differentiation 274 (CD274), neurotrophin receptor tyrosine kinase 1 (NTRK1), and rearranged during transfection (RET) occurred only in plasma. The majority of mutations in both samples were single-nucleotide variants. Deletions were found in EGFR, BRAF, and TP53 in ctDNA, whereas in tDNA, deletions were only found in EGFR. In ALK, single nucleic acid-site amplification occurred simultaneously in tissue and plasma, but insertions and copy number variations were detected only in plasma.
Conclusions:
Identifying ctDNA mutations by targeted sequencing in plasma is feasible, showing the clinical value of ctDNA-targeted sequencing in NSCLC patients when tumor tissue sampling is insufficient or even impossible.
Insights
Circulating tumor DNA (ctDNA) sequencing is a viable method for non-small cell lung cancer (NSCLC) patients with insufficient tissue samples. This approach aids in identifying key mutations for personalized treatment strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Circulating tumor DNA (ctDNA) analysis is gaining traction in clinical settings.
- Non-small cell lung cancer (NSCLC) diagnosis often faces challenges with inadequate tumor tissue samples.
Purpose of the Study:
- To evaluate the clinical utility of a minimally invasive ctDNA sequencing method for NSCLC.
- To assess ctDNA as a sensitive tool for next-generation sequencing when tumor tissue is insufficient.
Main Methods:
- Targeted DNA sequencing was performed on paired tissue biopsies and plasma samples from 60 NSCLC patients.
- Analysis focused on detecting mutations in 13 key driving genes.
Main Results:
- A 75.47% overall concordance rate was observed between tissue DNA (tDNA) and ctDNA.
- Epidermal growth factor receptor (EGFR) mutations were most frequent; some mutations (BRAF, CD274, NTRK1, RET) were exclusively found in ctDNA.
- Single-nucleotide variants were the predominant mutation type; deletions and copy number variations showed distinct patterns in ctDNA versus tDNA.
Conclusions:
- Targeted sequencing of ctDNA in plasma is a feasible and clinically valuable approach for NSCLC.
- ctDNA sequencing offers a crucial alternative when tumor tissue sampling is insufficient or impossible for molecular profiling.
