BRAF and KIT somatic mutations are present in amelanotic melanoma.
The genotypic profile of rare amelanotic melanomas (AMs) has been poorly investigated, thus preventing either an accurate identification as a distinctive melanoma subtype or therapy stratification. Here, we investigated the presence of the BRAF(V600E) mutation by real-time quantitative PCR and KIT mutations (exons 11 and 17) by sequencing analysis in 33 AMs. AMs included 'truly' amelanotic lesions (n = 19), with no melanin pigmentation upon dermoscopic inspection and hypomelanotic lesions (n = 14), by definition partially pigmented lesions showing a melanin pigmentation area of less than 25% of the total surface area. The frequency of the BRAF(V600E) mutation was 70.3% in the 33 cases, a percentage that increased to 89% when only the subgroup of thin melanomas (≤ 1 mm in thickness, n = 9) was considered. KIT mutations were found in 12.1% of AMs, all of which developed in nonacral sites. The identification of a relatively high frequency of BRAF(V600E) and KIT mutations in AMs may have important consequences for implementation of the novel targeted therapies now available to treat this life-threatening disease.
Department of Surgery and Translational Medicine, Division of Pathological Anatomy, University of Florence, Florence, Italy. daniela.massi@unifi.it
Daniela
D
Massi
Pamela
P
Pinzani
Lisa
L
Simi
Francesca
F
Salvianti
Vincenzo
V
De Giorgi
Maria A
MA
Pizzichetta
Francesco
F
Mirri
Agostino
A
Steffan
Claudio
C
Orlando
Marco
M
Santucci
Vincenzo
V
Canzonieri
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008297:Male; D018328:Melanoma, Amelanotic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf