Cutaneous Melanoma

MelArray detected a notably high number of alterations in the TERT promoter and CDKN2A genes, which were not captured by OFA and are of potential therapeutic relevance. In conclusion, MelArray enables a more comprehensive molecular characterization of cutaneous melanoma compared with a small generic cancer panel and may support more personalized therapeutic decision-making.

Conversely, PD-L1 and gender showed no consistent predictive value, whereas cutaneous immune-related adverse events and ctDNA reflected favorable and poor outcomes, respectively. These findings highlight the multifactorial nature of immunotherapy response and support the further development of integrated prognostic models to refine patient stratification and optimize treatment outcomes.

The recurrent coexistence of IDH1 mutations with MAPK pathway and TERT promoter alterations supports a potential cooperative role within melanoma oncogenesis. These findings are descriptive and hypothesis-generating, and further studies with larger cohorts are required to clarify the biological and clinical relevance of IDH1 mutations in melanoma.

P1/2, N=117, Recruiting, Georgiamune Inc | Trial completion date: Nov 2026 --> Nov 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=10, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | N=30 --> 10 | Trial primary completion date: Dec 2026 --> Dec 2027

P=N/A, N=12, Active, not recruiting, AdventHealth Translational Research Institute | Recruiting --> Active, not recruiting | N=20 --> 12 | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Aug 2025

P2, N=10, Active, not recruiting, UNICANCER | Trial completion date: Apr 2029 --> Mar 2026 | Trial primary completion date: Apr 2025 --> Mar 2026

The presence of MS appeared to correlate with worse clinical outcomes, as 67% of patients with MS died, compared to none without. Our findings expand the recognized molecular diversity of MBNs and provide insights into their biological behaviors, underscoring the clinical significance of identifying potential prognostic factors.

This case highlights the crucial role of molecular profiling in the diagnostic workup of intramedullary melanocytic lesions. The identification of GNAQ mutations, after the exclusion of other GNAQ-mutated primaries, supports a primary CNS origin, whereas BRAF mutations suggest a metastatic origin. Accurate diagnosis drastically alters the oncological management.

This functional inhibition persists following DNA damage or pharmacologic disruption of TP53 pathways, demonstrating that oncogenic BRAF constrains TP53 activity. These findings establish a protein interaction through which BRAFV600E functionally inactivates TP53 and reveal a mechanism by which melanoma bypasses TP53-mediated tumor suppression without requiring genetic alteration.

Furthermore, we identified a human orthologue of Dlx4os. Our findings highlight the potential of Dlx4os as both a biomarker and therapeutic target, capable of modulating melanoma's phenotypic plasticity to influence treatment response and metastasis.

Virtual screening (DrugBank) identified Dapagliflozin and Rivaroxaban, which were further evaluated by molecular dynamics (MD) simulations, binding free energy (MM/GBSA) calculations, and in vitro cytotoxicity using the MTT assay on B16F10 melanoma cells. Computational analyses predicted favorable binding for Dapagliflozin to IGF1R, and subsequent in vitro experiments confirmed its moderate cytotoxic effects on melanoma cells, supporting its further investigation as a potential repurposed therapeutic agent for melanoma. The online version contains supplementary material available at 10.1007/s40199-026-00598-x.