Histopathology in H&N pathologies in the third millennium

Vol. 117: Issue 2 - April 2025

KRAS/NRAS variants and copy number alterations prognostically stratify patients with sinonasal melanoma

Authors

Laura Libera , Nora Sahnane , Mario Turri-Zanoni , Fabiano Pettenon , Deborah Marchiori , Paolo Battaglia , Alberto Daniele Arosio , Daniela Furlan , Maurizio Bignami , Paolo Castelnuovo , Fausto Sessa , Carla Facco , Michele Cerati , Stefano La Rosa

Key words: Sinonasal melanoma, molecular analysis, KRAS, NRAS, copy number alterations
Publication Date: 2025-05-21

Abstract

Sino-nasal mucosal melanoma (SN-MM) is an aggressive and rare form of melanoma arising from mucosal melanocytes with pathogenesis unrelated to sun exposure. Conversely to cutaneous melanoma (CM), the molecular bases underling SN-MM development and progression are unclear, and no molecular predictive markers have been identified yet. To better define the molecular landscape of SN-MM, a retrospective series of 37 SN-MMs from 31 patients was analysed for both somatic mutations and cytogenetic alterations. The somatic mutation analysis identified the presence of a driver gene pathogenic variant in 54% of cases. In detail, mutually exclusive NRAS mutations were found in 42% of cases, KRAS mutations in 6%, and KIT mutations in 6% of cases. Remarkably, no BRAF mutations were detected. Patients with NRAS-mutated/KRAS-wild type (wt) melanomas showed better outcome than patients with NRAS-wt/KRAS-mutated melanomas, which were associated with multiple recurrences at local or regional sites. On the other hand, focusing on genomic alterations, copy number variants (loss of 1p36, loss of 3p/3q) were identified in 19% of SN-MMs, which showed poor overall survival and short disease-free survival with early metastatic dissemination. This work describes a new integrated characterization of both single nucleotide variants and, for the first time, genomic alteration in SN-MM, providing a new insight into molecular bases of these neoplasms and prompting further efforts for personalized clinical protocols according to tumour aggressiveness.

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Authors

Laura Libera - Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy

Nora Sahnane - Unit of Anatomic Pathology, Azienda Socio Sanitaria Territoriale (ASST) dei Sette Laghi, Varese, Italy

Mario Turri-Zanoni - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, University of Insubria, and ASST Sette- Laghi, Varese, Italy

Fabiano Pettenon - Unit of Anatomic Pathology, Azienda Socio Sanitaria Territoriale (ASST) dei Sette Laghi, Varese, Italy

Deborah Marchiori - Unit of Anatomic Pathology, Azienda Socio Sanitaria Territoriale (ASST) dei Sette Laghi, Varese, Italy

Paolo Battaglia - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, University of Insubria, and ASST Sette- Laghi, Varese, Italy

Alberto Daniele Arosio - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, University of Insubria, and ASST Sette- Laghi, Varese, Italy

Daniela Furlan - Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Unit of Anatomic Pathology, Azienda Socio Sanitaria Territoriale (ASST) dei Sette Laghi, Varese, Italy

Maurizio Bignami - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, University of Insubria, and ASST Sette-Laghi, Varese, Italy

Paolo Castelnuovo - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, University of Insubria, and ASST Sette- Laghi, Varese, Italy

Fausto Sessa - Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy

Carla Facco - Unit of Anatomic Pathology, Azienda Socio Sanitaria Territoriale (ASST) dei Sette Laghi, Varese, Italy

Michele Cerati - Unit of Anatomic Pathology, Azienda Socio Sanitaria Territoriale (ASST) dei Sette Laghi, Varese, Italy

Stefano La Rosa - Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Unit of Anatomic Pathology, Azienda Socio Sanitaria Territoriale (ASST) dei Sette Laghi, Varese, Italy

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Copyright

Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
Libera, L., Sahnane, N., Turri-Zanoni, M., Pettenon, F., Marchiori, D., Battaglia, P., Arosio, A. D., Furlan, D., Bignami, M., Castelnuovo, P., Sessa, F., Facco, C., Cerati, M., & La Rosa, S. (2025). KRAS/NRAS variants and copy number alterations prognostically stratify patients with sinonasal melanoma. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 117(2). Retrieved from https://www.pathologica.it/article/view/1347
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