title: The clinical response to vemurafenib in a patient with a rare BRAFV600DK601del mutation-positive melanoma.
abstract: BACKGROUND
  Mutations in the activation segment of the v-raf murine sarcoma viral oncogene homolog B (BRAF) gene are present in approximately 50% of melanomas. The selective BRAF inhibitor vemurafenib has demonstrated significant clinical benefits in patients with melanomas harboring the most common mutations (V600E, V600K and V600R). However, the clinical activity of BRAF inhibitors in patients with rare mutations of codon 600 and the surrounding codons has not been documented.
  
  
  METHODS
  We used the BRAF inhibitor vemurafenib to treat a patient presenting a rare p.V600_K601delinsD-mutated melanoma. An objective response was evidenced by two months of progression-free survival. By cloning and sequencing BRAF exon 15, we confirmed that a dual mutation was present on a single allele and thus resulted in a BRAFV(600DK601del) mutant protein. We also performed an in silico crystal structure analysis of the mutated protein, in order to characterize the nature of the putative interaction between vemurafenib and the mutant protein.
  
  
  CONCLUSIONS
  This clinical experience suggests that (i) patients with BRAFV(600DK601del)-mutation-positive melanoma can be treated successfully with the oral BRAF inhibitor vemurafenib and (ii) molecular screening in this context should encompass rare and complex mutations.
authors.affiliation: Laboratoire d'Oncobiologie moléculaire, Centre Hospitalier Universitaire Amiens Picardie, F-80054 Amiens, France. trudel.stephanie@chu-amiens.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Trudel
authors.forename: Norbert
authors.initials: N
authors.lastname: Odolczyk
authors.forename: Julie
authors.initials: J
authors.lastname: Dremaux
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toffin
authors.forename: Aline
authors.initials: A
authors.lastname: Regnier
authors.forename: Henri
authors.initials: H
authors.lastname: Sevestre
authors.forename: Piotr
authors.initials: P
authors.lastname: Zielenkiewicz
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Arnault
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gubler
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics*; D008958:Models, Molecular; D009362:Neoplasm Metastasis / Q000188:drug therapy; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D048493:Proto-Oncogene Proteins B-raf / Q000737:chemistry / Q000235:genetics*; D017384:Sequence Deletion; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf