Related Experiment Video
Updated: Jun 30, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Targeted next-generation sequencing of 491 lung cancers in clinical practice: Implications for future detection
Xiao-Dan Liu1, Yan Zhang1, Hui-Ying He1
1Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing, 100191, China.
Abstract:
Although lung cancer remains the most common cause of global cancer-related mortality, the identification of oncogenic driver alterations and the development of targeted drugs has dramatically altered the therapeutic landscape. In this retrospective study, we found that 97.7% samples carried at least one mutation in the 25 genes tested in our cohort. 53.6% samples were positive for EGFR mutations, followed by TP53 (41.1%), KRAS (11.8%), ERBB2 (4.3%). EGFR mutations were mainly found in female adenocarcinomas, while TP53 was mainly found in male non-adenocarcinomas. Significant differences can be found in the mutation rate of EGFR (60.9% vs 11.9%), KRAS (12.2% vs 25.0%), STK11 (1.5% vs 11.9%), FGFR3 (2.4% vs 0.0%) and ERBB4 (1.2% vs 6.1%) between adenocarcinoma in our cohort and TCGA-LUAD data (all p < 0.001). What's more, we found that the mutation of EGFR increased significantly from adenocarcinomas in situ (AIS, 21.4%) to microinvasive adenocarcinomas (MIA, 52.4%) and invasive adenocarcinomas (IA, 61.1%), while the mutation of ERBB2 dropped markedly from AIS (21.4%) to MIA (9.5%) and IA (4.1%). At last, comparations between targeted NGS and ARMS-based single gene test in the detection of EGFR showed a 94.6% consistence. In conclusion, targeted NGS can provide a comprehensive mutational profile of lung cancer. Considering the high mutation rate of EGFR in NSCLC of Asian populations, a specialized detection strategy should be conducted.
Insights
This study analyzed lung cancer mutations, finding high rates of EGFR and TP53 alterations. Targeted next-generation sequencing (NGS) offers a comprehensive approach for identifying these key mutations in non-small cell lung cancer (NSCLC).
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Lung cancer is a leading cause of cancer mortality globally.
- Advances in targeted therapies have improved treatment outcomes.
- Identifying oncogenic driver alterations is crucial for personalized medicine.
Purpose of the Study:
- To investigate the mutational landscape of lung cancer in a specific cohort.
- To compare mutation profiles with existing databases like TCGA-LUAD.
- To evaluate the efficacy of targeted next-generation sequencing (NGS) for mutation detection.
Main Methods:
- Retrospective analysis of lung cancer samples.
- Targeted sequencing of 25 key cancer-related genes.
- Comparison of mutation frequencies with The Cancer Genome Atlas (TCGA-LUAD) data.
- Evaluation of EGFR mutation detection concordance between NGS and ARMS-based tests.
Main Results:
- 97.7% of samples harbored at least one mutation in the tested genes.
- EGFR (53.6%) and TP53 (41.1%) were the most frequent mutations.
- Significant differences in mutation rates (EGFR, KRAS, STK11, FGFR3, ERBB4) were observed compared to TCGA-LUAD data.
- EGFR mutations increased with tumor invasiveness (AIS to IA), while ERBB2 mutations decreased.
- Targeted NGS showed 94.6% consistency with ARMS for EGFR mutation detection.
Conclusions:
- Targeted NGS provides a comprehensive mutational profile for lung cancer.
- Distinct mutation patterns exist between different lung adenocarcinoma subtypes.
- A specialized detection strategy is recommended for EGFR mutations in Asian populations due to high prevalence.
