Related Experiment Video
Updated: Jul 20, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Clinicogenomic Features and Targetable Mutations in NSCLCs Harboring BRAF Non-V600E Mutations: A Multi-Institutional
Tetsuya Sakai1, Shingo Matsumoto1, Yasuto Ueda2
1Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Introduction:
BRAF non-V600E mutations occur in 1% to 2% of NSCLCs. Because of their rarity, the clinical backgrounds and outcomes of cytotoxic chemotherapy or immunotherapy remain unclear, and no targeted therapies are approved for BRAF non-V600E-mutant NSCLC.
Methods:
In this multi-institutional prospective lung cancer genomic screening project (LC-SCRUM-Asia), we evaluated the clinicogenomic characteristics and therapeutic outcomes of BRAF non-V600E-mutant NSCLC.
Results:
From March 2015 to November 2021, a total of 11,929 patients with NSCLC were enrolled. BRAF mutations were detected in 380 (3.5%), including the V600E (class I) in 119 (31%) and non-V600E in 261; the non-V600E were functionally classified into class II (122, 32%), class III (86, 23%), and non-classes I to III. Smokers and having concurrent RAS gene family or TP53 mutations were more frequently associated with class II or III than with class I. In patients with class III as compared with class I, the progression-free survival in response to platinum-containing chemotherapies (median, 5.3 versus 11.5 mo, p < 0.01) and the overall survival (median, 14.5 versus 34.8 mo, p < 0.02) were significantly shorter. Furthermore, class IIa mutations were significantly more frequent in our Asian cohort than in previously reported cohorts. The clinicogenomic features associated with class IIa were similar to those associated with class I, and one patient with NSCLC with K601E had a good response to dabrafenib plus trametinib.
Conclusions:
Patients with NSCLCs with BRAF non-V600E, especially class III, were associated with poorer therapeutic outcomes than those with V600E. Furthermore, patients with NSCLC with class IIa had distinct clinicogenomic features, and further preclinical and clinical studies are needed to evaluate class IIa mutations as a therapeutic target.
Insights
BRAF non-V600E mutations in non-small cell lung cancer (NSCLC) patients, particularly class III, show poorer outcomes with chemotherapy. Class IIa mutations present unique features warranting further investigation for targeted therapy.
Area of Science:
- Oncology
- Genetics
- Genomics
Background:
- BRAF non-V600E mutations are rare in non-small cell lung cancer (NSCLC), accounting for 1-2% of cases.
- The clinical characteristics and treatment outcomes for BRAF non-V600E-mutant NSCLC are poorly understood.
- No targeted therapies are currently approved for this specific mutation type.
Purpose of the Study:
- To evaluate the clinicogenomic characteristics of BRAF non-V600E-mutant NSCLC.
- To assess the therapeutic outcomes of standard treatments in these patients.
- To identify potential therapeutic targets for BRAF non-V600E-mutant NSCLC.
Main Methods:
- A multi-institutional prospective study (LC-SCRUM-Asia) enrolled 11,929 NSCLC patients from March 2015 to November 2021.
- BRAF mutations were identified and functionally classified (V600E, class II, class III, etc.).
- Clinicogenomic data and treatment responses were analyzed.
Main Results:
- BRAF mutations were found in 3.5% of patients; 261 had non-V600E mutations (class II, III).
- Class II/III mutations were associated with smoking and concurrent RAS/TP53 mutations.
- Patients with class III mutations had significantly shorter progression-free and overall survival compared to class I (V600E).
- Class IIa mutations were more frequent in the Asian cohort and showed similar features to class I; one patient with K601E responded to targeted therapy.
Conclusions:
- BRAF non-V600E NSCLC, especially class III, is linked to inferior therapeutic outcomes compared to V600E.
- Class IIa mutations exhibit distinct clinicogenomic features.
- Further research is needed to explore class IIa mutations as potential therapeutic targets.
More Related Videos
11:15Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
10:16Employing Digital Droplet PCR to Detect BRAF V600E Mutations in Formalin-fixed Paraffin-embedded Reference Standard Cell Lines
Published on: October 8, 2015
