title: Distribution of TERT promoter mutations in primary and metastatic melanomas in Austrian patients.
abstract: BACKGROUND
  TERT promoter mutations were detected at high frequencies in several cancer types including melanoma. Previous reports showed that these recurrent mutations increase TERT gene expression and the use of TERT mutation status as prognostic factor was suggested.
  
  
  OBJECTIVE
  Here we screen a panel of 115 melanoma tumor samples from Austrian patients to evaluate the prevalence and distribution of TERT promoter mutations. The association with clinical and tumor characteristics and the effect on overall survival was analyzed.
  
  
  METHODS
  Genomic DNA from formalin-fixed paraffin-embedded tumor samples was isolated followed by PCR amplification, Sanger sequencing and statistical analysis.
  
  
  RESULTS
  We identified TERT promoter mutations in 63 of 115 (54.8%) tumor samples. No statistical significant difference in mutation frequency between primary (22/40 [55%]) and metastatic lesions (41/75 [54.7%]) was detected. BRAF-/NRAS-mutated tumors showed a higher frequency of TERT mutations (pT OR 2.24, 95% CI 0.56-9.02, p = 0.3) (met OR 2.74, 95% CI 0.98-7.66, p = 0.05). In primary melanoma, the presence of alterations in TERT was associated with the carrier status of a common single-nucleotide polymorphism rs2853669 (OR 4.55, CI 1.18-17.52, p = 0.03). In this patient cohort, TERT promoter mutations were not associated with clinical characteristics such as the presence of ulceration or Breslow thickness or showed an effect on overall survival.
  
  
  CONCLUSIONS
  Alterations in the TERT promoter region are one of the most frequent mutations in melanoma. Based on this analysis and preliminary evidence, prospective studies will be needed to evaluate the reliability of TERT promoter mutations as prognostic factors in melanoma.
authors.affiliation: Department of General Dermatology, Medical University Graz, Graz, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Ofner
authors.affiliation: Department of General Dermatology, Medical University Graz, Graz, Austria.|Translational Skin Cancer Research - TSCR, DKTK Partner Site Essen/Düsseldorf, German Cancer Research Consortium, University of Duisburg Essen, Universitätsstrasse 1, Essen, 45141, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Ritter
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Heidenreich
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Dermatology, University Hospital of Essen, Essen, Germany.
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
authors.affiliation: Department of Dermatology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Schrama
authors.affiliation: Department of General Dermatology, Medical University Graz, Graz, Austria. j.becker@dkfz.de.|Translational Skin Cancer Research - TSCR, DKTK Partner Site Essen/Düsseldorf, German Cancer Research Consortium, University of Duisburg Essen, Universitätsstrasse 1, Essen, 45141, Germany. j.becker@dkfz.de.|Department of Dermatology, University Hospital of Essen, Essen, Germany. j.becker@dkfz.de.
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
mesh_terms: D001317:Austria; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: Melanoma; Metastatic lesion; Primary tumor; TERT promotor mutation