Mutation Status in Sinonasal Mucosal Melanoma

Background: 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 common mutation frequencies in a large series of primary SNMMs.

Methods: Tumor cells were identified in regions with > 20% nuclei. Genomic DNA was extracted from 55 formalin-fixed paraffin-embedded tumors and screened for mutations by direct sequencing.

Results: Overall, 40% (22 out of 55) of SNMMs harbored mutations. In 20/22 (91%) mutations in these oncogenes occurred in a mutually exclusive manner. BRAF and KIT mutations were identified at a frequency of 8% (4/55) and 4% (2/55), respectively, whereas NRAS mutations were detected in 29% (16 out of 55) of the SNMMs. Four of the NRAS mutations were located in exon 1. Sporadic P53 and FGFR1 mutations were identified in 1 case each (2%). Mutation rates in these oncogenes were similar between melanomas located in the paranasal sinuses and in nasal cavity (46% and 38%, respectively, p = 0.5). In a multivariate analysis, patients with melanomas in the nasal cavity (HR=0.72, 95%CI- 0.31–0.86, 0 p = 0.04) and negative margins status (HR=0.22, 95%CI- 0.11–0.51, 0 p < 0.001) had a significantly better overall survival. The mutation status of the tumors showed no association with the overall survival.

Conclusion: 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. Still, a majority of SNMM has other unknown underlying oncogenic driver mutations that need to be addressed in future studies.