Activating BRAF mutations in eruptive melanocytic naevi.
BACKGROUND
Eruptive melanocytic naevi (EMN) are melanocytic proliferations developing rapidly on previously unaffected skin in association with various clinical scenarios, most commonly systemic immunosuppression. However, the exact mechanism leading to development of EMN is not understood. In particular, it is not known whether EMN harbour the BRAF mutations which occur frequently in melanoma and most common naevi.


OBJECTIVE
To evaluate whether activating BRAF mutations may play a role in genesis of EMN.


METHODS
Genomic DNA was isolated from 20 EMN from a patient treated with 6-mercaptopurine (6-MP). Primary BRAF genotyping was performed by allelespecific polymerase chain reaction, followed by validation using direct sequencing.


RESULTS
The BRAF V600E mutation was identified in 85% of EMN examined.


CONCLUSIONS
Our results implicate mutational activation of the BRAF–MAPK pathway as a factor in development of EMN in the setting of 6-MP treatment. The mechanism leading to development of EMN in this, and potentially other patients, may relate to synergistic mutagenic effects of thioguanines and ultraviolet (UV) A. Together with the documented importance of BRAF mutations in melanoma development and maintenance, these findings highlight the importance of UVA protection, especially in patients treated with thiopurines such as 6-MP.
Sekulic
A
A
Department of Dermatology, Mayo Clinic College of Medicine, Scottsdale, AZ 85259, USA. Sekulic@mayo.edu
Colgan
M B
MB
Davis
M D P
MD
DiCaudo
D J
DJ
Pittelkow
M R
MR
D000328:Adult; D004273:DNA, Neoplasm / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009508:Nevus, Pigmented / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf