title: KIT gene mutations and patterns of protein expression in mucosal and acral melanoma.
abstract: BACKGROUND
  Recently characterized KIT (CD117) gene mutations have revealed new pathways involved in melanoma pathogenesis. In particular, certain subtypes harbor mutations similar to those observed in gastrointestinal stromal tumors, which are sensitive to treatment with tyrosine kinase inhibitors.
  
  
  OBJECTIVE
  The purpose of this study was to characterize KIT gene mutations and patterns of protein expression in mucosal and acral melanoma.
  
  
  METHODS
  Formalin-fixed, paraffin-embedded tissues were retrieved from our archives. Histologic assessment included routine hematoxylin-eosin stains and immunohistochemical staining for KIT. Genomic DNA was used for polymerase chain reaction-based amplification of exons 11 and 13.
  
  
  RESULTS
  We identified 59 acral and mucosal melanoma cases, of which 78% showed variable levels of KIT expression. Sequencing of exons 11 and 13 was completed on all cases, and 4 (6.8%) mutant cases were isolated.
  
  
  CONCLUSIONS
  We successfully optimized conditions for the detection of KIT mutations and showed that 8.6% of mucosal and 4.2% of acral melanoma cases at our institution harbor KIT mutations; all mutant cases showed strong, diffuse KIT protein expression. Our case series represents the first Canadian study to characterize KIT gene mutations and patterns of protein expression in acral and mucosal melanoma.
authors.affiliation: Department of Anatomical Pathology, Sunnybrook Health Sciences Centre, Toronto, ON.
authors.forename: Suzan
authors.initials: S
authors.lastname: Abu-Abed
authors.forename: Nancy
authors.initials: N
authors.lastname: Pennell
authors.forename: Teresa
authors.initials: T
authors.lastname: Petrella
authors.forename: Frances
authors.initials: F
authors.lastname: Wright
authors.forename: Arun
authors.initials: A
authors.lastname: Seth
authors.forename: Wedad
authors.initials: W
authors.lastname: Hanna
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D060787:Neoplasm Grading; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D019009:Proto-Oncogene Proteins c-kit