title: KIT, NRAS and BRAF mutations in sinonasal mucosal melanoma: a study of 56 cases.
abstract: BACKGROUND
  Mucosal melanomas in the head and neck region are most frequently located in the nasal cavity and paranasal sinuses. Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas. The aim was to determine the KIT, NRAS and BRAF mutation frequencies in a large series of primary SNMMs.
  
  
  METHODS
  Laser capture microdissection was used to isolate tumour cells from 56 formalin-fixed paraffin-embedded tumours. The tumour cells were screened for KIT, NRAS and BRAF mutations by direct sequencing.
  
  
  RESULTS
  Overall, 21% (12 out of 56) of SNMMs harboured KIT, NRAS or BRAF mutations. Mutations in these oncogenes occurred in a mutually exclusive manner. Both KIT and BRAF mutations were identified at a similar frequency of 4% each (2 out of 56), whereas NRAS mutations were detected in 14% (8 out of 56) of the SNMMs. Four of the NRAS mutations were located in exon 1. Mutations in these oncogenes were significantly more common in melanomas located in the paranasal sinuses than in nasal cavity (P=0.045). In a multivariate analysis, patients with melanomas in the nasal cavity had a significantly better overall survival than those with tumours in the paranasal sinuses (P=0.027).
  
  
  CONCLUSIONS
  Our findings show that KIT and BRAF mutations, which are accessible for present targeted therapies, are only rarely present in SNMMs, whereas NRAS mutations seem to be relatively more frequent. The data show that majority of SNMMs harbour alterations in genes other than KIT, NRAS and BRAF.
authors.affiliation: Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden. sattar.zebary@ki.se
authors.forename: A
authors.initials: A
authors.lastname: Zebary
authors.forename: M
authors.initials: M
authors.lastname: Jangard
authors.forename: K
authors.initials: K
authors.lastname: Omholt
authors.forename: B
authors.initials: B
authors.lastname: Ragnarsson-Olding
authors.forename: J
authors.initials: J
authors.lastname: Hansson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016612:Paraffin Embedding; D010255:Paranasal Sinus Neoplasms / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D015996:Survival Rate
chemical_list: D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human