title: NRAS and BRAF mutations in melanoma-associated nevi and uninvolved nevi.
abstract: According to the prevailing multistep model of melanoma development, oncogenic BRAF or NRAS mutations are crucial initial events in melanoma development. It is not known whether melanocytic nevi that are found in association with a melanoma are more likely to carry BRAF or NRAS mutations than uninvolved nevi. By laser microdissection we were able to selectively dissect and genotype cells either from the nevus or from the melanoma part of 46 melanomas that developed in association with a nevus. In 25 cases we also genotyped a control nevus of the same patients. Available tissue was also immunostained using the BRAF(V600E)-mutation specific antibody VE1. The BRAF(V600E) mutation was found in 63.0% of melanomas, 65.2% of associated nevi and 50.0% of control nevi. No significant differences in the distribution of BRAF or NRAS mutations could be found between melanoma and associated nevi or between melanoma associated nevi and control nevi. In concordant cases immunohistochemistry showed a higher expression (intensity of immunohistochemistry) of the mutated BRAF(V600E)-protein in melanomas compared to their associated nevi. In this series the presence of a BRAF- or NRAS mutation in a nevus was not associated with the risk of malignant transformation. Our findings do not support the current traditional model of stepwise tumor progression.
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Tschandl
authors.forename: Anna Sophie
authors.initials: AS
authors.lastname: Berghoff
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.forename: Sebastian
authors.initials: S
authors.lastname: Burgstaller-Muehlbacher
authors.forename: Hubert
authors.initials: H
authors.lastname: Pehamberger
authors.forename: Ichiro
authors.initials: I
authors.lastname: Okamoto
authors.forename: Harald
authors.initials: H
authors.lastname: Kittler
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D009508:Nevus, Pigmented / Q000235:genetics* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human