title: Implementation of a companion diagnostic in the clinical laboratory: the BRAF example in melanoma.
abstract: A companion diagnostic test provides information that is essential for the safe and effective use of a corresponding therapeutic product as indicated in the drug instructions. The implementation of a companion diagnostic follows the rules of a molecular test for somatic mutations in a routine clinical laboratory environment and needs guidance on practical aspects, including the choice of the proper analytical method and the procedures for internal and external quality controls. Selection of the appropriate assay for detection of genetic alterations depends on several factors: the type of mutation under study, the sample to be assayed and its preparation procedure. In addition, the results of a molecular assay require a complex interpretation process of the analytical data as the patient's genotype, the translation of the identified variant into a predicted phenotype and knowledge on restrictions of the method used. In relation to these aspects herein we report an opinion paper of the Working Group Personalized Laboratory Medicine jointly constituted by the European Federation of Laboratory Medicine (EFLM) and by the European Society of Pharmacogenomics and Theranostics (ESPT) using, as an example, the BRAF genotype analysis in tumor tissue samples for identification of melanoma patients that can benefit treatment with BRAF inhibitors. The manuscript is focused on the following aspects: i) medical rationale, ii) methodologies of analysis, iii) laboratory performance evaluation and iv) the laboratory specific report for the clinicians. The critical evaluation of these aspects would be useful for the implementation of a companion diagnostic in the clinical laboratory.
authors.affiliation: Department of Clinical and Experimental Biomedical Sciences, University of Florence, Italy. Electronic address: irene.mancini@unifi.it.
authors.forename: Irene
authors.initials: I
authors.lastname: Mancini
authors.affiliation: Department of Clinical and Experimental Biomedical Sciences, University of Florence, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Pinzani
authors.affiliation: Department of Clinical and Experimental Biomedical Sciences, University of Florence, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Simi
authors.affiliation: Department of Biochemistry Faculty of Health Sciences, University of Southern Denmark, Vejle Hospital, Vejle, Denmark.
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
authors.affiliation: Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vermeersch
authors.affiliation: Genomic Unit for the Diagnosis of Human Pathologies, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Resta
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; Department of Clinical Pharmacology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
authors.affiliation: Department of Clinical Chemistry, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Ron
authors.initials: R
authors.lastname: van Schaik
authors.affiliation: Department of Clinical and Experimental Biomedical Sciences, University of Florence, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Pazzagli
mesh_terms: D019411:Clinical Laboratory Techniques; D005838:Genotype; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Companion diagnostics; Melanoma; Molecular analysis; Targeted therapy