title: Exon 15 BRAF mutations are uncommon in melanomas arising in nonsun-exposed sites.
abstract: OBJECTIVE
  An activating point mutation of the BRAF oncogene has been identified in a high proportion of cutaneous nevi and cutaneous melanomas, but its frequency in melanomas arising from the mucosa of head and neck is unknown.
  
  
  METHODS
  We tested 17 malignant mucosal melanomas of the head and neck for the thymine (T)-->adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using direct sequencing and a newly developed assay that uses a novel primer extension method (Mutector assay). We also tested 21 cutaneous melanomas, including 13 arising from sun-exposed sites and 8 from a nonsun-exposed site, the vulvar skin.
  
  
  RESULTS
  The 1796T-->A mutation was detected in only 1 (6%) of the sinonasal melanomas. As for cutaneous melanomas, a BRAF mutation was detected in 8 (62%) of the tumors arising in sun-exposed sites but in none (0%) of vulvar melanomas.
  
  
  CONCLUSIONS
  In contrast to cutaneous melanomas arising in sun-exposed sites, mucosal melanomas of the head and neck do not frequently harbor an activating mutation of BRAF. This finding additionally supports the view that the various subtypes of melanoma are not equivalent and that distinct genetic alterations may underlie well recognized differences in risk factors and behavioral patterns. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new strategies are developed that target specific genetic alterations.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.forename: Eli
authors.initials: E
authors.lastname: Rosenbaum
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Begum
authors.forename: David
authors.initials: D
authors.lastname: Goldenberg
authors.forename: Clemens
authors.initials: C
authors.lastname: Esche
authors.forename: Ofer
authors.initials: O
authors.lastname: Lavie
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
mesh_terms: D000225:Adenine; D004247:DNA / Q000378:metabolism; D005091:Exons; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D009152:Mutagenicity Tests; D009154:Mutation; D020125:Mutation, Missense; D009506:Nevus / Q000235:genetics*; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000235:genetics*; D013941:Thymine / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D004247:DNA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000225:Adenine; D013941:Thymine