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Updated: Jan 20, 2026
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
The association between BRAF mutation class and clinical features in BRAF-mutant Chinese non-small cell lung cancer
Quan Lin1, Haoran Zhang2, Huaxin Ding3
1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Campus, Ouhai District, Wenzhou, 325015, Zhejiang, China.
Background:
BRAF mutations occur in 2-4% non-small cell lung cancer (NSCLC) patients and can be categorized into three functional classes based on signaling mechanism and kinase activity: RAS-independent kinase-activating V600 monomers (class 1), RAS-independent kinase-activating dimers (class 2) and RAS-dependent kinase-inactivating heterodimers (class 3). The association between functional classes and clinical features in Chinese NSCLC patients remains unexplored. Our multi-center study aimed to survey the BRAF mutation rate and analyze the associated clinical features in this population.
Methods:
Capture-based sequencing data of either plasma or tissue samples obtained from 8405 Chinese stage I-IV NSCLC patients were retrospectively analyzed.
Results:
BRAF mutations were detected in 238 patients, revealing an overall mutation rate of 2.8%. Among them, 32%, 21% and 13% had BRAF mutant class 1, 2 and 3 respectively. The remaining 34% had other BRAF mutations. V600 (32%) and G469 (13%) were the two most predominant BRAF mutations. Patients with class 2 and 3 mutations were more likely to have concurrent KRAS mutations (P = 0.001). Collectively, BRAF mutations, including non-class 1-3 mutations, were more likely to occur in males (P < 0.01). However, females were more likely to harbor class 1 mutations (P < 0.02). We also compared the overall survival (OS) of first-line chemotherapy-treated advanced-stage patients and revealed comparable OS among the three groups.
Conclusion:
Our study revealed a 2.8% BRAF mutation rate in Chinese NSCLC patients. Our data also showed a male predominance when all BRAF mutations were considered collectively, and a female predominance for class 1 mutations. Furthermore, BRAF V600E is less likely to have concurrent KRAS mutations comparing to the other two classes.
Insights
This study found a 2.8% BRAF mutation rate in Chinese non-small cell lung cancer (NSCLC) patients. BRAF mutations showed distinct clinical associations, with males more likely to have mutations overall and females more likely to have class 1 mutations.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- BRAF mutations are found in 2-4% of non-small cell lung cancer (NSCLC) patients.
- BRAF mutations are classified into three functional groups based on signaling and kinase activity.
- The clinical associations of BRAF functional classes in Chinese NSCLC patients are not well understood.
Purpose of the Study:
- To determine the BRAF mutation rate in Chinese NSCLC patients.
- To analyze the clinical features associated with different BRAF functional classes in this population.
Main Methods:
- Retrospective analysis of capture-based sequencing data from 8405 Chinese NSCLC patients (stages I-IV).
- Identification and classification of BRAF mutations.
- Statistical analysis of mutation rates, clinical features, and survival data.
Main Results:
- BRAF mutations were detected in 2.8% of patients (238/8405).
- Class 1, 2, and 3 mutations accounted for 32%, 21%, and 13% of BRAF mutations, respectively.
- BRAF mutations were more common in males, while class 1 mutations were more prevalent in females. Class 2 and 3 mutations were associated with concurrent KRAS mutations.
Conclusions:
- The BRAF mutation rate in Chinese NSCLC patients is 2.8%.
- Distinct clinical associations exist for BRAF mutations, including gender predominance for overall and class 1 mutations.
- BRAF V600E mutations are less likely to co-occur with KRAS mutations compared to other BRAF classes.
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