Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomas

Br J Cancer. 2008 Dec 16;99(12):2065-9. doi: 10.1038/sj.bjc.6604791. Epub 2008 Nov 18.


Recent data suggested an increased frequency of KIT aberrations in mucosal melanomas, whereas c-KIT in most types of cutaneous melanomas does not appear to be of pathogenetic importance. However, studies investigating the status of the KIT gene in larger, well-characterised groups of patients with mucosal melanomas are lacking. We analysed 44 archival specimens of 39 well-characterised patients with mucosal melanomas of different locations. c-KIT protein expression was determined by immunhistochemistry, KIT gene mutations were analysed by PCR amplification and DNA sequencing of exons 9, 11, 13, 17 and 18. c-KIT protein expression could be shown in 40 out of 44 (91%) tumours in at least 10% of tumour cells. DNA sequence analysis of the KIT was successfully performed in 37 patients. In 6 out of 37 patients (16%) KIT mutations were found, five in exon 11 and one in exon 18. The presence of mutations in exon 11 correlated with a significant stronger immunohistochemical expression of c-KIT protein (P=0.015). Among the six patients with mutations, in two patients the primary tumour was located in the head/neck region, in three patients in the genitourinary tract and in one patient in the anal/rectal area. In conclusion, KIT mutations can be found in a subset of patients with mucosal melanomas irrespective of the location of the primary tumour. Our data encourage therapeutic attempts with tyrosine kinase inhibitors blocking c-KIT in these patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • Melanoma / enzymology*
  • Melanoma / genetics*
  • Melanoma / pathology
  • Middle Aged
  • Molecular Sequence Data
  • Mucous Membrane / enzymology*
  • Mutation / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Proto-Oncogene Proteins c-kit / analysis*
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Transition Temperature


  • Proto-Oncogene Proteins c-kit
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf