C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma

Virchows Arch. 2008 Jan;452(1):27-32. doi: 10.1007/s00428-007-0524-2. Epub 2007 Dec 8.

Abstract

C-kit is a trans-membrane receptor tyrosine kinase (RTK) encoded by the proto-oncogene KIT located at 4q11-12. Gain-of-function mutations arising to c-kit activation independent of its ligand were observed in various tumors related to germ cells, mast cells, and interstitial cells of Cajal. C-kit also participates in melanocyte development; hence, its involvement in oral mucosal melanoma (OMM) tumorigenesis was investigated. Immunohistochemistry and mutation analysis were performed using 18 cases of human primary OMM. Results revealed 16 cases positive to c-kit protein. Atypical melanocytes expressed c-kit. All in situ components expressed c-kit, but only four cases exhibited intense expression in the invasive component. Missense mutations were observed in four cases, and two of those correlated with increased protein expression. C-kit expression in atypical melanocytes suggests the role of c-kit in the early stage of OMM tumorigenesis. C-kit protein expression correlated with activating mutations indicating the pertinent role of the proto-oncogene KIT in the tumorigenesis of OMM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Mutational Analysis
  • DNA, Neoplasm / analysis
  • Humans
  • Immunohistochemistry
  • Melanocytes / metabolism
  • Melanocytes / pathology
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Molecular Sequence Data
  • Mouth Mucosa / metabolism*
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Mutation, Missense*
  • Polymorphism, Single-Stranded Conformational
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Sequence Analysis, DNA

Substances

  • DNA, Neoplasm
  • Proto-Oncogene Proteins c-kit