Prognostic Roles of BRAF, KIT, NRAS, IGF2R and SF3B1 Mutations in Mucosal Melanomas

Abstract

Background: The prognostic value of commonly recurrent mutations remains unclear in mucosal melanomas. Methods: Clinicopathologic parameters of 214 cases of mucosal melanomas diagnosed in 1989–2020 in several clinical institutions were analyzed. NRAS, KIT, BRAF, IGF2R and SF3B1 mutational analyses by Sanger sequencing and next generation sequencing-based assay were performed in a subset of cases. Results: Of the triple (BRAF, NRAS, NF1)-negative cases, APC, KIT and KRAS are detected mainly in sinonasal, vulvovaginal and anorectal melanomas, respectively. NRAS, KIT, BRAF, IGF2R and SF3B1 mutations are detected in 19% (37/198), 22% (44/197), 12% (25/201), 16% (22/138) and 15% (20/133) of cases, respectively. In univariate analyses, advanced stage (p = 0.016), 65 years or older (p = 0.048) and presence of ulceration (p = 0.027) are significantly correlated with worse overall survival (OS), respectively. NRAS mutation significantly correlates with worse OS (p = 0.028) and worse melanoma-specific survival (MSS) (p = 0.03) for all cases of mucosal melanomas. In multivariate analyses, NRAS mutation remains as an independent predictor of worse OS (p = 0.036) and worse MSS (p = 0.024). Conclusion: NRAS mutation is a predictor of worse survival, independent of stage in mucosal melanomas. The significance of frequently mutated IGF2R in mucosal melanomas remains unclear.