title: NRAS mutations are more prevalent than KIT mutations in melanoma of the female urogenital tract--a study of 24 cases from the Netherlands.
abstract: OBJECTIVE
  The aim of this study was to evaluate a series of primary melanomas of the female urogenital tract for oncogenic mutations in KIT, NRAS and BRAF in order to identify patients who may be amenable to targeted therapy.
  
  
  METHODS
  We reviewed twenty-four cases of female urogenital tract melanomas and used Sanger sequencing analysis for the detection of oncogenic mutations in exons 9, 11, 13, and 17 of KIT; exons 2 and 3 of NRAS; and exon 15 of BRAF.
  
  
  RESULTS
  Twenty-four patients were included: fourteen vaginal melanomas, four cervical melanomas, five urethral melanomas and one vulvar melanoma. NRAS mutations (4/24, 21%) were more prevalent than KIT mutations (1/24, 4%), while BRAF mutations were absent. Three of four NRAS mutations were present in vaginal melanomas (21%), mainly affecting codon 61 (3/4). They were mutually exclusive with the KIT mutation. The KIT mutation was present in a vaginal melanoma and affected exon 17.
  
  
  CONCLUSIONS
  Melanomas of the female urogenital tract relatively commonly harbor mutations in NRAS; this makes NRAS an interesting therapeutic target for these patients in the advanced setting. KIT mutations were rare in our study in contrast to some previous reports. We cannot exclude that anatomical site-related differences and/or population related differences in KIT mutation frequency exist within urogenital tract melanomas.
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands. Electronic address: Ilse.vanEngen-vanGrunsven@radboudumc.nl.
authors.forename: Adriana C H
authors.initials: AC
authors.lastname: van Engen-van Grunsven
authors.affiliation: Department of Pathology, Canisius Wilhelmina Hospital, P.O. Box 9015, Nijmegen, 6500 GS, The Netherlands.
authors.forename: Heidi V N
authors.initials: HV
authors.lastname: Küsters-Vandevelde
authors.affiliation: Department of Obstetrics and Gynecology, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands.
authors.forename: Joanne
authors.initials: J
authors.lastname: De Hullu
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands.
authors.forename: Lucette M
authors.initials: LM
authors.lastname: van Duijn
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Rijntjes
authors.affiliation: Department of Pathology, Leiden University Medical Center, P.O. Box 9600, Leiden, 2300 RC, The Netherlands.
authors.forename: Judith V M G
authors.initials: JV
authors.lastname: Bovée
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands.
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands.
authors.forename: Willeke A M
authors.initials: WA
authors.lastname: Blokx
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D005260:Female; D005557:Formaldehyde; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005833:Genital Neoplasms, Female / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D016612:Paraffin Embedding; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012189:Retrospective Studies; D016707:Tissue Fixation; D014516:Ureteral Neoplasms / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D005557:Formaldehyde; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: BRAF; KIT; MAPK pathway; NRAS; Urogenital tract melanoma; Vaginal melanoma