Prognostic Roles of <i>BRAF</i>, <i>KIT</i>, <i>NRAS</i>, <i>IGF2R</i> and <i>SF3B1</i> Mutations in Mucosal Melanomas

• Main Authors: Joanna P. Wróblewska, Dora Dias-Santagata, Adam Ustaszewski, Cheng-Lin Wu, Masakazu Fujimoto, M. Angelica Selim, Wojciech Biernat, Janusz Ryś, Andrzej Marszalek, Mai P. Hoang
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Cells
• Subjects: mucosal melanoma; vulvovaginal; sinonasal; anorectal; <i>NRAS</i>; <i>KIT</i>
• Online Access: https://www.mdpi.com/2073-4409/10/9/2216

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. <i>NRAS</i>, <i>KIT</i>, <i>BRAF</i>, <i>IGF2R</i> and <i>SF3B1</i> mutational analyses by Sanger sequencing and next generation sequencing-based assay were performed in a subset of cases. Results: Of the triple (<i>BRAF</i>, <i>NRAS</i>, <i>NF1</i>)-negative cases, <i>APC</i>, <i>KIT</i> and <i>KRAS</i> are detected mainly in sinonasal, vulvovaginal and anorectal melanomas, respectively. <i>NRAS</i>, <i>KIT</i>, <i>BRAF</i>, <i>IGF2R</i> and <i>SF3B1</i> 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 (<i>p</i> = 0.016), 65 years or older (<i>p</i> = 0.048) and presence of ulceration (<i>p</i> = 0.027) are significantly correlated with worse overall survival (OS), respectively. <i>NRAS</i> mutation significantly correlates with worse OS (<i>p</i> = 0.028) and worse melanoma-specific survival (MSS) (<i>p</i> = 0.03) for all cases of mucosal melanomas. In multivariate analyses, <i>NRAS</i> mutation remains as an independent predictor of worse OS (<i>p</i> = 0.036) and worse MSS (<i>p</i> = 0.024). Conclusion: <i>NRAS</i> mutation is a predictor of worse survival, independent of stage in mucosal melanomas. The significance of frequently mutated <i>IGF2R</i> in mucosal melanomas remains unclear.