Atypical <i>BRAF</i> and <i>NRAS</i> Mutations in Mucosal Melanoma

• Main Authors: Nicolas Dumaz, Fanélie Jouenne, Julie Delyon, Samia Mourah, Armand Bensussan, Céleste Lebbé
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: Cancers
• Subjects: mucosal melanoma; <i>BRAF</i>; <i>NRAS</i>; mutations; MAPK; targeted therapies
• Online Access: https://www.mdpi.com/2072-6694/11/8/1133

Primary mucosal melanomas represent a minority of melanomas, but have a significantly worse prognosis than cutaneous melanomas. A better characterization of the molecular pathogenesis of this melanoma subtype could help us understand the risk factors associated with the development of mucosal melanomas and highlight therapeutic targets. Because the Mitogen-Activated Protein Kinase (MAPK) pathway plays such a significant role in melanoma development, we explore v-raf murine sarcoma viral oncogene homolog B (<i>BRAF)</i> and neuroblastoma RAS viral oncogene homolog (<i>NRAS)</i> mutations in mucosal melanoma and compare them to the mutation profiles in cutaneous melanoma and other tumors with <i>BRAF</i> and <i>NRAS</i> mutations. We show that in addition to being less frequent, <i>BRAF</i> and <i>NRAS</i> mutations are different in mucosal melanoma compared to cutaneous melanomas. Strikingly, the <i>BRAF</i> and <i>NRAS</i> mutation profiles in mucosal melanoma are closer to those found in cancers such as lung cancer, suggesting that mutations in mucosal melanoma could be linked to some genotoxic agents that remain to be identified. We also show that the atypical <i>BRAF</i> and <i>NRAS</i> mutations found in mucosal melanomas have particular effects on protein activities, which could be essential for the transformation of mucosal melanocytes.