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.
AIMS: 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.
CONCLUSION: 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.