title: Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations.
abstract: OBJECTIVE
  Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease. Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more frequent KIT mutations than cutaneous melanomas. For the majority of mucosal melanomas oncogenic driver mutations remain unknown.
  
  
  RESULTS
  In our study, 75 tumor tissues from patients diagnosed with mucosal melanoma were analyzed, applying a targeted next generation sequencing panel covering 29 known recurrently mutated genes in melanoma. NF1 and RAS mutations were identified as the most frequently mutated genes occurring in 18.3% and 16.9% of samples, respectively. Mutations in BRAF were identified in 8.4% and KIT in 7.0% of tumor samples.
  
  
  CONCLUSIONS
  Our study identifies NF1 as the most frequently occurring driver mutation in mucosal melanoma. RAS alterations, consisting of NRAS and KRAS mutations, were the second most frequent mutation type. BRAF and KIT mutations were rare with frequencies below 10% each. Our data indicate that in mucosal melanomas RAS/NF1 alterations are frequent, implying a significant pathogenetic role for MAPK and potentially PI3K pathway activation in these tumors.
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Cosgarea
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Sucker
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Livingstone
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Hospital Leipzig, Germany.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Ziemer
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Utikal
authors.affiliation: Department of Dermatology, Elbe Klinikum Buxtehude, Buxtehude, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Mohr
authors.affiliation: Department of Dermatology, Klinikum Augsburg, Augsburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Pfeiffer
authors.affiliation: Department of Dermatology, Saarland University Medical School, Homburg/Saar, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pföhler
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Hillen
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Horn
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Griewank
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roesch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D025542:Neurofibromin 1 / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D008565:Membrane Proteins; D025542:Neurofibromin 1; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: NF1; RAS; melanoma; mucosal melanoma; sequencing