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Updated: Oct 26, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Genomic Profiling of Circulating Tumor DNA from Patients with Extensive-Stage Small Cell Lung Cancer Identifies
Jing Yang1,2, Xiangyun Wang3, Jingli Lu1,2
1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Abstract:
Comprehensive genomic profiling may help uncover potentially actionable alterations in small cell lung cancer (SCLC) patients who have progressed on standard chemotherapy. However, tissue procurement may be extremely challenging for extensive-stage patients. We aimed to investigate the possibility of genomic profiling and detecting actionable alterations from blood in Chinese SCLC patients. Blood samples collected from extensive-stage SCLC pateints were subjected to circulating tumor DNA (ctDNA) extraction and targeted-next generation sequencing (NGS) using a 150-gene panel. A total of 1,300 aberrations were detected in 128 genes and 89.2% (116/130) patients harbored at least one oncogenic alteration. The most frequently mutated genes included TP53 (82.3%), RB1 (56.2%), LRP1B (40.8%) etc. and 54.6% of the patients had concurrent TP53/RB1 mutations. The RTK/RAS/RAF axis was the most frequently mutated oncogenic pathway. Samples harboring alterations in the DNA damaging repair (DDR), Notch, PI3K/mTOR, RTK/RAS/RAF, and Wnt pathways exhibited significantly higher blood tumor mutational burden (bTMB) than their wildtype counterparts. Classification based on OncoKB criteria detected potentially actionable alterations in about 50% of the population, half of which were bTMB-H and bMSI-H, indicating response to immune checkpoint inhibitors. Alterations in the RTK/RAS/RAF, DDR, and PI3K/mTOR also suggested potential sensitivity to matched targeted therapies or emerging investigational agents. Blood-based panel NGS is promising for delineating genomic landscape of SCLC and may also shed some light on treatment selection for Chinese SCLC patients.
Insights
Blood tests can identify genetic changes in advanced small cell lung cancer (SCLC) patients. This genomic profiling reveals actionable alterations, aiding treatment decisions for Chinese SCLC patients.
Area of Science:
- Oncology
- Genomics
- Translational Research
Background:
- Comprehensive genomic profiling (CGP) aids in identifying actionable alterations in advanced small cell lung cancer (SCLC) patients post-chemotherapy.
- Tissue biopsy for genomic analysis is challenging in extensive-stage SCLC patients.
Purpose of the Study:
- To evaluate the feasibility of genomic profiling using blood samples (circulating tumor DNA - ctDNA) in Chinese SCLC patients.
- To detect actionable genomic alterations and understand the genomic landscape in this population.
Main Methods:
- Targeted next-generation sequencing (NGS) on a 150-gene panel was performed on ctDNA from extensive-stage SCLC patients.
- Analysis focused on identifying aberrations, oncogenic alterations, and specific gene mutations (e.g., TP53, RB1).
- Blood tumor mutational burden (bTMB) and microsatellite instability (bMSI) were assessed.
Main Results:
- 1,300 aberrations were detected across 128 genes in 130 patients.
- 89.2% of patients had at least one oncogenic alteration, with TP53 (82.3%) and RB1 (56.2%) being the most frequent.
- Approximately 50% of patients had actionable alterations, including high bTMB and bMSI, suggesting potential response to immunotherapy.
Conclusions:
- Blood-based targeted NGS is a viable method for genomic profiling in Chinese SCLC patients.
- This approach can identify actionable alterations and inform treatment selection, including targeted therapies and immune checkpoint inhibitors.
