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.
The detection of V600E BRAF mutation in melanoma is fundamental since here BRAF inhibitors represent an effective treatment.,Non-V600E BRAF mutations that may also respond are not detected by certain screening methods.,Thus, knowledge about detection of these mutations is needed.,A total of 276 tumour samples from 174 melanoma patients were investigated for BRAF mutations by pyrosequencing.,Rare mutations were confirmed by capillary sequencing and compared with findings from COBAS test and immunohistochemistry using a novel BRAF antibody.,Melanoma type, localisation, and survival were summarised.,BRAF mutations were found in 43% of patients (124 tumours in 75 patients).,Among those, 14 patients (18.7%) exhibited rare mutations.,The V600EK601del and V600DK601del mutations have never been described before in melanoma.,Furthermore, V600K, V600E2, and V600D, V600G, V600R, and L597S mutations were detected.,Mutations were not detected by COBAS test in 7 out of these 14 patients and immunohistochemistry only reliably detected patients with the V600E2 and V600EK601del mutation.,Accurate diagnosis of rare BRAF mutations is crucial.,We show that pyrosequencing is accurate, highly sensitive, reliable, and time saving to detect rare BRAF mutations.,Missing these rare variant mutations would exclude a subset of patients from available effective BRAF-targeting therapy.