title: BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular level.
abstract: OBJECTIVE
  Anorectal melanoma (AM) is a rare but highly malignant tumor, displaying histologic and immunohistochemical features very similar to cutaneous melanoma (CM). Because BRAF mutations were recently identified in the majority of CM and nevi, we investigated AM for BRAF mutations and mutations of NRAS , an additional component of the MAPK-signalling pathway.
  
  
  METHODS
  DNA from formalin-fixed and paraffin-embedded AM was PCR amplified and sequenced.
  
  
  RESULTS
  We detected BRAF mutations in 2 of 19 cases and NRAS mutations in none of the cases. Mutations in exon 15 of BRAF were present in only 1 tumor (1 of 19 cases). The A1800T base exchange represented a novel mutation and resulted in a K600N transition in an AM from a 96-year-old white man who presented with rectal bleeding and painful sitting of a few weeks' duration. The second positive AM case, a 69-year-old white man who presented with painless rectal bleeding and clinical symptoms of an intestinal constipation showed a novel missense mutation (C1327T leading to R443W conversion) in BRAF exon 11. None of the AM cases displayed the oncogenic V599E mutation preponderating in CM.
  
  
  CONCLUSIONS
  With regard to the frequency of V599E BRAF mutations, AM significantly differs from CM (P < or = .0001), which suggests that BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular level.
authors.affiliation: Institute of Pathology, University of Heidelberg, D-69210 Heidelberg, Germany. Burkhard_Helmke@med.uni-heidelberg.de
authors.forename: Burkhard M
authors.initials: BM
authors.lastname: Helmke
authors.forename: Jan
authors.initials: J
authors.lastname: Mollenhauer
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Marianne
authors.initials: M
authors.lastname: Thome
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Gassler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wahl
authors.forename: Stefan
authors.initials: S
authors.lastname: Lyer
authors.forename: Annemarie
authors.initials: A
authors.lastname: Poustka
authors.forename: Herwart F
authors.initials: HF
authors.lastname: Otto
authors.forename: Martin
authors.initials: M
authors.lastname: Deichmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf