Melanocyte development provides an excellent model for studying more complex developmental processes.,Melanocytes have an apparently simple aetiology, differentiating from the neural crest and migrating through the developing embryo to specific locations within the skin and hair follicles, and to other sites in the body.,The study of pigmentation mutations in the mouse provided the initial key to identifying the genes and proteins involved in melanocyte development.,In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches.,This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma.,Summary: This Review discusses melanocyte development and differentiation, melanocyte stem cells, and the role of the melanocyte lineage in diseases such as melanoma.
Mucosal melanomas in the head and neck region are most frequently located in the nasal cavity and paranasal sinuses.,Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas.,The aim was to determine the KIT, NRAS and BRAF mutation frequencies in a large series of primary SNMMs.,Laser capture microdissection was used to isolate tumour cells from 56 formalin-fixed paraffin-embedded tumours.,The tumour cells were screened for KIT, NRAS and BRAF mutations by direct sequencing.,Overall, 21% (12 out of 56) of SNMMs harboured KIT, NRAS or BRAF mutations.,Mutations in these oncogenes occurred in a mutually exclusive manner.,Both KIT and BRAF mutations were identified at a similar frequency of 4% each (2 out of 56), whereas NRAS mutations were detected in 14% (8 out of 56) of the SNMMs.,Four of the NRAS mutations were located in exon 1.,Mutations in these oncogenes were significantly more common in melanomas located in the paranasal sinuses than in nasal cavity (P=0.045).,In a multivariate analysis, patients with melanomas in the nasal cavity had a significantly better overall survival than those with tumours in the paranasal sinuses (P=0.027).,Our findings show that KIT and BRAF mutations, which are accessible for present targeted therapies, are only rarely present in SNMMs, whereas NRAS mutations seem to be relatively more frequent.,The data show that majority of SNMMs harbour alterations in genes other than KIT, NRAS and BRAF.