title: Clinical characteristics and outcome of patients with lung cancer harboring BRAF mutations.
abstract: BACKGROUND
  BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations are identified in approximately 2% of non-small cell lung cancer (NSCLC). Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far.
  
  
  METHODS
  Here we took advantage of the French National Cancer Institute Program of systematic molecular profiling of metastatic lung cancer, to collect clinical characteristics and analyze the outcome of consecutive patients with NSCLC harboring BRAF mutations at the Lyon University Hospital laboratory between February 2012 and October 2014. Especially, we compared those variables with that of patients with EGFR-, BRAF-, KRAS-, HER2-, PIK3CA- wild-type NSCLCs.
  
  
  RESULTS
  Among 2690 patients with genotyped NSCLC during the study period, BRAF mutations were identified in 80 (3%) cases, consisting of V600E substitution in 42 (53%) cases; non-V600E mutation were observed in 38 (48%) cases. Concurrent mutations were not observed in case of BRAF V600 mutation, and were identified in 5 patients with BRAF non-V600E mutations, in all cases consisting of KRAS mutations. Non-V600E mutations were more likely to be observed in smokers, as compared V600E mutations. There was no significant difference in age, histologic type, performance status, and stage at diagnosis between cases of V600E and non-V600E mutations. Overall survival did not significantly differ in BRAF wild-type, V600E, and non-V600E patients.
  
  
  CONCLUSIONS
  This one of the largest series of patients with BRAF mutant NSCLC. Our clinical data suggest that BRAF mutations define specific subsets of patients with NSCLC; while their oncogenic nature is yet to be established in lung cancer, especially for non-V600E mutations, the value of BRAF mutations to predict the efficacy of targeted agents remains unclear.
authors.affiliation: Acute Respiratory Medicine and Thoracic Oncology Department, Hôpital Lyon Sud, Hospices Civils de Lyon, 69495 Pierre Bénite, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Tissot
authors.affiliation: Acute Respiratory Medicine and Thoracic Oncology Department, Hôpital Lyon Sud, Hospices Civils de Lyon, 69495 Pierre Bénite, France; EMR 3738 Therapeutic Targeting in Oncology, Lyon sud-Charles Mérieux Faculty of Medicine, Lyon 1 University, 69600 Oullins, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Couraud
authors.affiliation: Radiotherapy Unit, Lyon Cancer Center Léon Bérard, 69008, Lyon, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Tanguy
authors.affiliation: Molecular Diagnostics Laboratory, Hôpital Édouard-Herriot, 69437 Lyon cedex 03, France.
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Bringuier
authors.affiliation: Respiratory Medicine and Thoracic Oncology Service, Hôpital Louis Pradel, Hospices Civils de Lyon, 69677 Lyon cedex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.affiliation: Acute Respiratory Medicine and Thoracic Oncology Department, Hôpital Lyon Sud, Hospices Civils de Lyon, 69495 Pierre Bénite, France. Electronic address: pierre-jean.souquet@chu-lyon.fr.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Souquet
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010091:Oximes / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016019:Survival Analysis
chemical_list: D007093:Imidazoles; C117307:KRAS protein, human; D010091:Oximes; D047428:Protein Kinase Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); C561627:dabrafenib
keywords: BRAF mutations; EGFR mutations; Lung cancer; Smoking; V600E mutation