Cutaneous melanoma subtypes show different BRAF and NRAS mutation frequencies.
OBJECTIVE
BRAF mutations are present in two thirds of cutaneous melanomas and many of the rest have NRAS mutations. However, cutaneous melanoma is a heterogeneous disease with many clinicopathologic subtypes. Of these, the majority fits into four categories: superficial spreading, nodular, lentigo maligna, and acral lentiginous melanoma (ALM). Thus far, there is very limited data combining BRAF and NRAS mutation analysis to explore differences between cutaneous melanoma subtypes. The aim of this study was to address this issue.


METHODS
The frequency of BRAF and NRAS hotspot mutations, in exons 15 and 2, respectively, was assessed in 59 cutaneous melanomas comprising superficial spreading, nodular, lentigo maligna, and ALM using single-strand conformational polymorphism and RFLP-PCR analysis.


RESULTS
Only 2 of 21 (9.5%) ALM showed BRAF exon 15 mutation compared with 9 of 14 (64.3%) superficial spreading malignant melanomas, 4 of 11 (36.4%) nodular melanomas, and 7 of 13 (53.4%) lentigo maligna melanomas (P < 0.01). However, our key finding is that the combined analysis of BRAF exon 15 and NRAS exon 2 showed that there were no significant differences in the overall mutation frequency between subtypes. In particular, 9 of 19 (47.4%) ALM without BRAF exon 15 mutation had an NRAS exon 2 mutation.


CONCLUSIONS
We show that the overall BRAF/NRAS frequency in mutation hotspots is not significantly different among cutaneous melanoma subtypes. These data show that mitogen-activated protein kinase pathway activation may be important in all major subtypes of cutaneous melanoma, although the mechanism by which this is achieved varies.
Saldanha
Gerald
G
Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom. gss4@le.ac.uk
Potter
Linda
L
Daforno
Philip
P
Pringle
J Howard
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D005260:Female; D005787:Gene Frequency; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf