title: Large-scale analysis of KIT aberrations in Chinese patients with melanoma.
abstract: OBJECTIVE
  KIT aberrations were described in acral and mucosal melanomas in largely Caucasian populations. Asian populations are more prone to develop acral and mucosal than cutaneous melanomas, and may harbor a high frequency of KIT aberrations.
  
  
  METHODS
  Melanoma subtypes (n = 502) were analyzed histologically to determine melanoma subtype. Tissue samples were analyzed for mutations in exons 9, 11, 13, 17, and 18 of KIT gene in genomic DNA by PCR amplification and Sanger sequencing. The copy numbers of the KIT gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry.
  
  
  RESULTS
  The most common melanoma subtypes were acral (38.4%) and mucosal (33.3%) melanomas in this population. The overall incidence of somatic mutations within the KIT gene was 10.8% (54/502), and all subtypes of melanoma contained KIT mutations. Increases in KIT gene copy numbers were correlated to CD117 overexpression. The genetic mutations of KIT were unrelated to the age, gender, stage, thickness, and ulceration of primary melanomas. Importantly, the overall survival of melanoma patients with KIT mutations (P = 0.001) or with KIT aberrations (mutation plus amplification, P = 0.0002) was significantly shorter than that of patients without such alterations.
  
  
  CONCLUSIONS
  In China, the prevalent melanomas are acral and mucosal melanomas. KIT mutations are detected in all melanoma subtypes. Our study suggests that increases in KIT gene copy numbers, but not KIT mutations, may be correlated to CD117 overexpression. For the first time, our study suggests that genetic KIT aberration is an adverse prognostic factor for melanoma.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Kong
authors.forename: Lu
authors.initials: L
authors.lastname: Si
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Haifu
authors.initials: H
authors.lastname: Li
authors.forename: Xinan
authors.initials: X
authors.lastname: Sheng
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Cui
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Chi
authors.forename: Siming
authors.initials: S
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.forename: Lili
authors.initials: L
authors.lastname: Mao
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D014408:Biomarkers, Tumor / Q000378:metabolism; D018389:Codon, Nonsense; D005260:Female; D018628:Gene Dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D015999:Multivariate Analysis; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D013472:Sunlight / Q000009:adverse effects; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018389:Codon, Nonsense; D019009:Proto-Oncogene Proteins c-kit