BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs.
BACKGROUND
Malignant melanoma arising from different body compartments may be associated with differing aetiological factors and clinical behaviour, and may manifest diverse molecular genetic profiles. Although many studies have focused on cutaneous melanoma, little is known of mucosal and other types of melanoma. In particular, malignant melanoma of soft parts is different from other melanomas in many respects, yet manifests a common melanocytic differentiation. Mutation of BRAF is now known to be common in cutaneous melanomas, and raises possible new therapeutic options of anti-RAF treatment for these patients. Few data are available for non-cutaneous melanomas.


OBJECTIVE
To study the incidence of BRAF and NRAS mutations in melanomas arising in diverse internal organs.


METHODS
Fifty one melanomas from various internal organs were investigated for BRAF and NRAS mutation by direct DNA sequencing.


RESULTS
BRAF and NRAS mutations were found in two and five mucosal melanomas arising from the aerodigestive and female genital tracts (n = 36). Their occurrence is mutually exclusive, giving a combined mutation incidence rate of 19.4% in mucosal melanomas. Both BRAF and NRAS mutations were absent in malignant melanoma of soft parts (n = 7). BRAF mutation was also absent in uveal melanoma (n = 6), but was seen in two of five cutaneous melanomas. The incidence of BRAF or combined BRAF/NRAS mutations in all non-cutaneous groups was significantly lower than published rates for cutaneous melanomas.


CONCLUSIONS
Each melanoma subtype may have a unique oncogenetic pathway of tumour development, and only a small fraction of non-cutaneous melanomas may benefit from anti-RAF treatment.
Wong
C W
CW
Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong.
Fan
Y S
YS
Chan
T L
TL
Chan
A S W
AS
Ho
L C
LC
Ma
T K F
TK
Yuen
S T
ST
Leung
S Y
SY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004067:Digestive System Neoplasms / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D005833:Genital Neoplasms, Female / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics; D014604:Uveal Neoplasms / Q000235:genetics
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D048493:Proto-Oncogene Proteins B-raf