title: C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma.
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.
authors: Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors: Rosario S
authors: RS
authors: Rivera
authors: Hitoshi
authors: H
authors: Nagatsuka
authors: Mehmet
authors: M
authors: Gunduz
authors: Beyhan
authors: B
authors: Cengiz
authors: Esra
authors: E
authors: Gunduz
authors: Chong Huat
authors: CH
authors: Siar
authors: Hidetsugu
authors: H
authors: Tsujigiwa
authors: Ryo
authors: R
authors: Tamamura
authors: Kok Ng
authors: KN
authors: Han
authors: Noriyuki
authors: N
authors: Nagai
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit