Absence of V599E BRAF mutations in desmoplastic melanomas.
BACKGROUND
Desmoplastic melanoma is an uncommon variant of cutaneous melanoma that mimics soft tissue sarcoma both clinically and morphologically. An activating point mutation of the BRAF oncogene has been identified in a high proportion of conventional cutaneous melanomas, but its frequency in the desmoplastic subtype is not known.


METHODS
The authors tested 12 desmoplastic melanoma specimens for the thymine (T)-->adenine (A) missense mutation at nucleotide 1796 of the BRAF gene using a newly developed assay that employs a novel primer extension method. They also tested 57 vertical growth phase cutaneous nondesmoplastic melanoma specimens.


RESULTS
The 1796 T-->A mutation was detected in 23 of the 57 conventional cutaneous melanoma specimens but in none of the 12 desmoplastic melanoma specimens (40% vs. 0%; P=0.0006, Fisher exact 2-tailed test).


CONCLUSIONS
The relative importance of BRAF mutational activation in melanocytic tumorigenesis clearly was not the same across the various subtypes of melanoma, even for melanomas of cutaneous origin that are associated with sun exposure. In contrast to conventional cutaneous melanomas, the desmoplastic variant frequently did not harbor an activating mutation of BRAF. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new therapeutic strategies are developed that target specific genetic alterations.
Davison
Jon M
JM
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
Rosenbaum
Eli
E
Barrett
Terry L
TL
Goldenberg
David
D
Hoque
Mohammad O
MO
Sidransky
David
D
Westra
William H
WH
D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf