title: Prevalence of BRAF V600E mutation in Chinese melanoma patients: large scale analysis of BRAF and NRAS mutations in a 432-case cohort.
abstract: BACKGROUND
  Mutations of NRAS and BRAF have been described in Caucasian melanomas. However, the status and the clinical significance of BRAF and NRAS mutations in the Asian population have not been investigated on a large scale.
  
  
  METHODS
  Melanoma samples (n=432) were analysed for mutations in exons 11 and 15 of the BRAF gene, and exons 1 and 2 of the NRAS gene in genomic DNA by polymerase chain reaction (PCR) amplification and Sanger sequencing. Mutations of BRAF and NRAS genes were correlated to clinicopathologic features and prognosis of the patients.
  
  
  RESULTS
  The incidence of somatic mutations within the BRAF and NRAS genes was 25.5% (110/432) and 7.2% (31/432), respectively. Among the 110 patients with BRAF mutations, 98 patients (89.1%) had V600E mutations. Melanomas without chronic sun-induced damage (Non-CSD) were more likely (P<0.01) to show BRAF mutations while NRAS mutation frequency was unbiased between melanoma subtypes. Patients with genetic mutations in BRAF (P<0.01) or NRAS (P=0.04) gene are more likely to have ulceration as compared to patients without BRAF or NRAS mutations, respectively. Both BRAF (P=0.003) and NRAS mutations (P=0.031) are inversely correlated to overall survival.
  
  
  CONCLUSIONS
  BRAF mutation is frequent while mutations in NRAS gene are rare. The most prevalent BRAF mutation type is V600E. Patients with mutations in BRAF or NRAS gene are frequently present with ulceration, and mutation in BRAF or NRAS gene is indicator for poor prognosis. Our study may warrant a clinical trial of kinase inhibitors targeting BRAF V600E in Chinese and Asian melanoma patients.
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: Lu
authors.initials: L
authors.lastname: Si
authors.forename: Yan
authors.initials: Y
authors.lastname: Kong
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
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: Lili
authors.initials: L
authors.lastname: Mao
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D059645:Mutation Rate; D020125:Mutation, Missense; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D014633:Valine / Q000235:genetics
chemical_list: D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine