BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular level.
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.
Helmke
Burkhard M
BM
Institute of Pathology, University of Heidelberg, D-69210 Heidelberg, Germany. Burkhard_Helmke@med.uni-heidelberg.de
Mollenhauer
Jan
J
Herold-Mende
Christel
C
Benner
Axel
A
Thome
Marianne
M
Gassler
Nikolaus
N
Wahl
Wolfgang
W
Lyer
Stefan
S
Poustka
Annemarie
A
Otto
Herwart F
HF
Deichmann
Martin
M
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*
D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf