title: Assessment of clinical parameters associated with mutational status in metastatic malignant melanoma: a single-centre investigation of 141 patients.
abstract: BACKGROUND
  Inhibitors of the mutated, constitutively activated BRAF protein have shown efficacy in the treatment of metastatic melanoma in clinical trials. Mutation analysis especially of the BRAF, NRAS and KIT genes is essential to identify patients suitable for targeted therapies and has been introduced into routine patient care.
  
  
  OBJECTIVE
  To correlate mutational status with clinical parameters including age, skin type, number of melanocytic naevi, primary tumour location, chronic sun damage and exposure to ultraviolet (UV) irradiation. The overall aim was to define subgroups with an increased or decreased likelihood of gene mutations. Additionally, the impact of activating BRAF mutations on clinical course was investigated.
  
  
  METHODS
  In a single-centre, retrospective approach, mutation analysis was performed on patients with metastatic malignant melanoma. Clinical parameters were correlated with molecular findings. The total sun-burden score was assessed using a validated standardized questionnaire.
  
  
  RESULTS
  The analysis included 141 patients with metastatic melanoma. Forty-four per cent of patients had activating BRAF mutations and were significantly younger than patients with wild-type BRAF or with NRAS mutations. KIT mutations were detected in only 3% of the patients. BRAF-mutated melanomas developed preferentially in intermittently sun-exposed areas of the body, and patients had significantly more melanocytic naevi. Once patients had progressed into stage IV disease, survival times were identical for those with BRAF-mutated and BRAF wild-type tumours.
  
  
  CONCLUSIONS
  Mutations of the BRAF gene are correlated with younger age, a higher number of melanocytic naevi and a tumour location in intermittently UV-exposed skin. Signs of chronic photodamage are not indicative of mutational status. Patients with metastatic melanoma with BRAF mutations showed a nonsignificant tendency to progress later to stage IV disease, but once metastases were present the prognosis was identical to that with BRAF wild-type tumours.
authors.affiliation: Department of Dermatology and Venereology, Skin Cancer Center, University Hospital of Cologne, Kerpener Str. 62, 50927 Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schlaak
authors.forename: A
authors.initials: A
authors.lastname: Bajah
authors.forename: T
authors.initials: T
authors.lastname: Podewski
authors.forename: N
authors.initials: N
authors.lastname: Kreuzberg
authors.forename: W
authors.initials: W
authors.lastname: von Bartenwerffer
authors.forename: E
authors.initials: E
authors.lastname: Wardelmann
authors.forename: S
authors.initials: S
authors.lastname: Merkelbach-Bruse
authors.forename: R
authors.initials: R
authors.lastname: Büttner
authors.forename: C
authors.initials: C
authors.lastname: Mauch
authors.forename: P
authors.initials: P
authors.lastname: Kurschat
mesh_terms: D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012189:Retrospective Studies; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects
chemical_list: D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf