title: Detection of BRAF V600 mutations in melanoma: evaluation of concordance between the Cobas® 4800 BRAF V600 mutation test and the methods used in French National Cancer Institute (INCa) platforms in a real-life setting.
abstract: Vemurafenib is approved for the treatment of metastatic melanoma in patients with BRAF V600 mutation. In pivotal clinical trials, BRAF testing has always been done with the approved cobas 4800 BRAF test. In routine practice, several methods are available and are used according to the laboratories usual procedures. A national, multicenter, non-interventional study was conducted with prospective and consecutive collection of tumor samples. A parallel evaluation was performed in routine practice between the cobas 4800 BRAF V600 mutation test and home brew methods (HBMs) of 12 national laboratories, labelled and funded by the French National Cancer Institute (INCa). For 420 melanoma samples tested, the cobas method versus HBM showed a high concordance (93.3%; kappa = 0.86) in BRAF V600 genotyping with similar mutation rates (34.0% versus 35.7%, respectively). Overall, 97.4% and 98.6% of samples gave valid results using the cobas and HBM, respectively. Of the 185 samples strictly fulfilling the cobas guidelines, the concordance rate was even higher (95.7%; kappa = 0.91; 95%CI [0.85; 0.97]). Out of the 420 samples tested, 28 (6.7%) showed discordance between HBM and cobas. This prospective study shows a high concordance rate between the cobas 4800 BRAF V600 test and home brew methods in the routine detection of BRAF V600E mutations.
authors: Department of Pharmacology-Genetics, AP-HP, Saint-Louis Hospital, Paris, France; INSERM UMRS 976 Paris, F-75010, France.
authors: Samia
authors: S
authors: Mourah
authors: Department of Biochemistry, Nantes University Hospital, Nantes, France.
authors: Marc G
authors: MG
authors: Denis
authors: Department of Molecular Biology and Biochemistry, Lille Regional University Hospital, Lille, France.
authors: Fabienne Escande
authors: FE
authors: Narducci
authors: Department of Biology-Pathology, Montpellier University Hospital, Montpellier, France.
authors: Jérôme
authors: J
authors: Solassol
authors: Department of Tumor Biology, Alexis Vautrin Center, Vandoeuvre les Nancy, France.
authors: Jean-Louis
authors: JL
authors: Merlin
authors: Department of Pathology-Cytopathology, Rouen University Hospital, Rouen, France.
authors: Jean-Christophe
authors: JC
authors: Sabourin
authors: Laboratory of Pathology and Cytopathology, Edouard Herriot Hospital, Lyon, France; Department of Biology and Pathology, Gustave Roussy Hospital, Villejuif, France.
authors: Jean-Yves
authors: JY
authors: Scoazec
authors: Department of Cancer Biology, Marseille Nord University Hospital, Marseille, France.
authors: L'Houcine
authors: L
authors: Ouafik
authors: Department of Pathology, Ambroise Paré Hospital, Boulogne-Billancourt, France.
authors: Jean-François
authors: JF
authors: Emile
authors: Department of Microbiology and Molecular Biology, Colmar hospital, Colmar, France.
authors: Remy
authors: R
authors: Heller
authors: Roche, Boulogne-Billancourt, France.
authors: Claude
authors: C
authors: Souvignet
authors: Roche, Boulogne-Billancourt, France.
authors: Loïc
authors: L
authors: Bergougnoux
authors: Department of Tumor Biology, Bordeaux University Hospital, Bordeaux, France.
authors: Jean-Philippe
authors: JP
authors: Merlio
mesh_terms: D005838:Genotype; D006801:Humans; D007753:Laboratories / Q000592:standards; D016015:Logistic Models; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis* / Q000235:genetics; D011933:Reagent Kits, Diagnostic; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics
chemical_list: D011933:Reagent Kits, Diagnostic; D048493:Proto-Oncogene Proteins B-raf