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Atypical BRAF and NRAS Mutations in Mucosal Melanoma

1
INSERM, U976, Team 1, Human Immunology Pathophysiology & Immunotherapy (HIPI), F-75010 Paris, France
2
Institut de Recherche Saint Louis (IRSL), Université de Paris, F-75010 Paris, France
3
Département de Pharmacogénomique, Hôpital Saint Louis, AP-HP, F-75010 Paris, France
4
Département de Dermatologie, Hôpital Saint Louis, AP-HP, F-75010 Paris, France
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1133; https://doi.org/10.3390/cancers11081133
Received: 5 July 2019 / Revised: 6 August 2019 / Accepted: 7 August 2019 / Published: 8 August 2019
(This article belongs to the Special Issue Oncogenic Forms of BRAF as Cancer Driver Genes)
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 (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations in mucosal melanoma and compare them to the mutation profiles in cutaneous melanoma and other tumors with BRAF and NRAS mutations. We show that in addition to being less frequent, BRAF and NRAS mutations are different in mucosal melanoma compared to cutaneous melanomas. Strikingly, the BRAF and NRAS 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 BRAF and NRAS mutations found in mucosal melanomas have particular effects on protein activities, which could be essential for the transformation of mucosal melanocytes. View Full-Text
Keywords: mucosal melanoma; BRAF; NRAS; mutations; MAPK; targeted therapies mucosal melanoma; BRAF; NRAS; mutations; MAPK; targeted therapies
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Dumaz, N.; Jouenne, F.; Delyon, J.; Mourah, S.; Bensussan, A.; Lebbé, C. Atypical BRAF and NRAS Mutations in Mucosal Melanoma. Cancers 2019, 11, 1133.

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Cancers, EISSN 2072-6694, Published by MDPI AG
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