Journal of Clinical Oncology · 2011 · 690 citations · 31 references
MedicineGeneticsOncologyCancer GeneticsMolecular OncologyNeoplasiaCancer Molecular PathologyLung CancerMalignant NeoplasmsMolecular Classification Of TumorsMutation AnalysisOncogene MutationsAlk Rearrangement TestingBraf V600 MutationsBraf V600e MutationCancer Mutation AnalysisKras Mutation TestingLung AdenocarcinomaNon-small Cell Lung Cancer TherapyOncogenic Mutation Spectrum
PURPOSE: BRAF mutations occur in non-small-cell lung cancer. Therapies targeting BRAF mutant tumors have recently been identified. We undertook this study to determine the clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. PATIENTS AND METHODS: We reviewed data from consecutive patients with lung adenocarcinoma whose tumors underwent BRAF, EGFR, and KRAS mutation testing as well as fluorescence in situ hybridization for ALK rearrangements. Patient characteristics including age, sex, race, performance status, smoking history, stage, treatment history, and overall survival were collected. RESULTS: Among 697 patients with lung adenocarcinoma, BRAF mutations were present in 18 patients (3%; 95% CI, 2% to 4%). The BRAF mutations identified were V600E (50%), G469A (39%), and D594G (11%). Mutations in EGFR were present in 24%, KRAS in 25%, and ALK translocations in 6%. In contrast to patients with EGFR mutations and ALK rearrangements who were mostly never smokers, all patients with BRAF mutations were current or former smokers (P < .001). The median overall survival of advanced-stage patients with BRAF mutations was not reached. In comparison, the median overall survival of patients with EGFR mutations was 37 months (P = .73), with KRAS mutations was 18 months (P = .12), and with ALK rearrangements was not reached (P = .64). CONCLUSION: BRAF mutations occur in 3% of patients with lung adenocarcinoma and occur more commonly in current and former smokers. The incidence of BRAF mutations other than V600E is significantly higher in lung cancer than in melanoma.
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