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Updated: Apr 20, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Clinical characteristics and course of 63 patients with BRAF mutant lung cancers
Anya M Litvak1, Paul K Paik, Kaitlin M Woo
1Departments of *Medicine, Thoracic Oncology Service, Division of Solid Tumor Oncology, †Epidemiology and Biostatistics, and ‡Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
Introduction:
Mutant BRAF is a driver oncogene found in 2% of lung adenocarcinomas and represents a target for therapy. We examined the clinical characteristics and course of patients with lung adenocarcinomas harboring BRAF mutations.
Methods:
We identified patients with lung adenocarcinomas harboring BRAF mutations between 2009 and 2013 detected using a mass spectrometry-based polymerase chain reaction genotyping assay of hot-spot mutations involving codons corresponding to amino acids V600, D594, and G469 of BRAF. Patient characteristics and treatment outcomes were analyzed. Overall survival (OS) was compared with stage-matched patients with KRAS and EGFR mutant lung adenocarcinomas.
Results:
Sixty-three patients were diagnosed with BRAF mutant lung adenocarcinomas between 2009 and 2013 (V600, 36; non-V600, 27). The majority of patients with BRAF mutations were smokers (92%), although patients with V600 mutations were more likely to be light/never-smokers compared with patients with non-V600 mutations (42% versus 11%; p = 0.007). Of the 32 patients with early-stage disease, six (19%; 95% confidence interval 7%-36%) developed second primary lung cancers harboring KRAS mutations. Patients with advanced V600 mutant lung adenocarcinomas had a better survival from diagnosis compared with those with non-V600 mutant lung adenocarcinomas (3-year OS: 24% versus 0%; p < 0.001).
Conclusions:
This is the largest series of patients with BRAF mutant lung cancers described. Most patients were heavy smokers. Nineteen percent of patients with early-stage BRAF mutant lung cancers developed second primary lung cancers harboring KRAS mutations. Patients with advanced lung adenocarcinomas harboring V600 mutations have an improved OS compared with those with non-V600 mutations.
Insights
BRAF-mutated lung adenocarcinomas are often linked to smoking. Patients with V600 BRAF mutations show improved survival, and a subset develops KRAS-mutated lung cancers.
Area of Science:
- Oncology
- Genetics
- Pulmonology
Background:
- BRAF mutations are key drivers in 2% of lung adenocarcinomas, presenting therapeutic targets.
- Understanding the clinical profile of BRAF-mutated lung adenocarcinomas is crucial for treatment strategies.
Purpose of the Study:
- To investigate the clinical characteristics and outcomes of lung adenocarcinoma patients with BRAF mutations.
- To compare overall survival (OS) in BRAF-mutated lung cancer with KRAS and EGFR mutations.
Main Methods:
- Identified BRAF-mutated lung adenocarcinomas (2009-2013) using mass spectrometry-based PCR genotyping.
- Analyzed patient demographics, smoking history, and treatment outcomes.
- Compared OS with stage-matched KRAS and EGFR mutant lung adenocarcinomas.
Main Results:
- Sixty-three BRAF-mutated lung adenocarcinomas were identified (36 V600, 27 non-V600).
- Most patients were smokers (92%); V600 mutations were more common in light/never-smokers (42% vs. 11%).
- 19% of early-stage patients developed secondary KRAS-mutated lung cancers. Advanced V600 mutant lung adenocarcinomas had better 3-year OS (24% vs. 0%).
Conclusions:
- This study represents the largest cohort of BRAF-mutated lung cancers.
- BRAF-mutated lung cancers predominantly affect smokers; early-stage disease carries a risk of secondary KRAS-mutated lung cancers.
- Advanced V600 BRAF-mutated lung adenocarcinomas demonstrate superior overall survival compared to non-V600 mutations.
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