title: KIT gene mutations and copy number in melanoma subtypes.
abstract: OBJECTIVE
  We recently identified a KIT exon 11 mutation in an anorectal melanoma of a patient who had an excellent response to treatment with imatinib. To determine the frequency of KIT mutations across melanoma subtypes, we surveyed a large series of tumors.
  
  
  METHODS
  One hundred eighty-nine melanomas were screened for mutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. A subset of cases was evaluated for BRAF and NRAS mutations. Immunohistochemistry was done to assess KIT (CD117) expression.
  
  
  RESULTS
  KIT mutations were detected in 23% (3 of 13) of acral melanomas, 15.6% (7 of 45) of mucosal melanomas, 7.7% (1 of 13) of conjunctival melanomas, 1.7% (1 of 58) of cutaneous melanomas, and 0% (0 of 60) of choroidal melanomas. Almost all the KIT mutations were of the type predicted to be imatinib sensitive. There was no overlap with NRAS mutations (11.1% of acral and 24.3% of mucosal tumors) or with BRAF mutations (absent in mucosal tumors). Increased KIT copy number was detected in 27.3% (3 of 11) of acral and 26.3% (10 of 38) of mucosal melanomas, but was less common among cutaneous (6.7%; 3 of 45), conjunctival (7.1%; 1 of 14), and choroidal melanomas (0 of 28). CD117 expression, present in 39% of 105 tumors representing all melanoma types, did not correlate with either KIT mutation status or KIT copy number.
  
  
  CONCLUSIONS
  Our findings confirm that KIT mutations are most common in acral and mucosal melanomas but do not necessarily correlate with KIT copy number or CD117 expression. Screening for KIT mutations may open up new treatment options for melanoma patients.
authors.affiliation: Oregon Cancer Institute, Oregon Health & Science University, Portland, Oregon 97239, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Beadling
authors.forename: Erick
authors.initials: E
authors.lastname: Jacobson-Dunlop
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.forename: Claudia
authors.initials: C
authors.lastname: Le
authors.forename: Andrea
authors.initials: A
authors.lastname: Warrick
authors.forename: Janice
authors.initials: J
authors.lastname: Patterson
authors.forename: Ajia
authors.initials: A
authors.lastname: Town
authors.forename: Amy
authors.initials: A
authors.lastname: Harlow
authors.forename: Frank
authors.initials: F
authors.lastname: Cruz
authors.forename: Sharl
authors.initials: S
authors.lastname: Azar
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rubin
authors.forename: Susan
authors.initials: S
authors.lastname: Muller
authors.forename: Rob
authors.initials: R
authors.lastname: West
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
mesh_terms: D018628:Gene Dosage; D011905:Genes, ras; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf