Morpho-Molecular Assessment Indicates New Prognostic Aspects and Personalized Therapeutic Options in Sinonasal...

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Sinonasal melanoma is a rare malignancy with limited understanding of its molecular characteristics.
• Current systemic treatments for metastatic sinonasal melanoma follow guidelines for cutaneous melanoma.
• Targetable BRAF mutations are infrequent in sinonasal melanoma compared to cutaneous melanoma.

Purpose of the Study:

• To investigate the molecular profile of primary sinonasal melanomas.
• To correlate molecular findings with histological and clinical features.
• To identify potential prognostic markers and personalized treatment strategies.

Main Methods:

• Analysis of 19 primary sinonasal melanomas.
• Utilized a custom melanoma-specific next-generation sequencing (NGS) panel (MelArray) targeting 190 genes.
• Correlated molecular data with histological and clinical features.

Main Results:

• Predominant mutations were observed in NRAS (25%); KIT or BRAF p.V600 mutations were not detected.
• Tumor mutational burden was generally low.
• High copy number variations (CNVs) were linked to DNA-repair gene alterations and reduced distant metastasis-free survival (p = 0.005).
• Monomorphic morphology was significantly associated with worse disease-specific survival (p < 0.001), independent of molecular aberrations.

Conclusions:

• Sinonasal melanoma exhibits a distinct molecular profile, primarily featuring NRAS mutations.
• High CNVs and specific morphological features are associated with poorer survival outcomes.
• Molecular profiling is crucial for identifying potential therapeutic targets and guiding personalized treatment approaches for sinonasal melanoma.