Mutation status among patients with sinonasal mucosal melanoma and its impact on survival

Background: Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas and lacks well-characterised molecular markers. Our aim was to determine the frequencies of common mutations and examine their utility as molecular markers in a large series of primary SNMMs. Methods: SNMM patients seen at our institution from August 1991 through July 2016 were identified. Genomic DNA was extracted from 66 formalin-fixed paraffin-embedded tumours and screened for mutations by direct sequencing. We investigated the association of mutations with clinicopathological features and survival outcomes. Results: Overall, 41% (27 out of 66) of the SNMMs harboured mutations. BRAF and KIT mutations were identified in 8% (five patients) and 5% (three patients) of SNMMs, respectively, whereas NRAS mutations were detected in 30% (20 patients) of SNMMs. Mutation rates in these oncogenes were similar between SNMMs located in the paranasal sinuses and those in the nasal cavity (30% and 13%, respectively, P = 0.09). In a multivariate analysis, patients with negative margins had significantly better overall survival (hazard ratio 5.43, 95% confidence interval 1.44-21.85, P = 0.01) and disease-specific survival (hazard ratio 21.9, 95% confidence interval 3.71-180, P = 0.0004). The mutation status of the tumours showed no association with survival outcomes. Conclusions: In SNNM, mutation status does not affect survival outcomes, but NRAS mutations are relatively frequent and could be targeted in this disease by MEK inhibitors.