Staging of Mucosal Melanoma of the Head and Neck

associated-melanoma in which arises from benign nevi, creates the unique opportunity to study the molecular mechanisms that drive early cancer initiation and progression.Methods: We used the recently published technique snPATHO-seq [1] which allows the RNA sequencing of single nuclei from FFPE archived tissue.Analysing nevus-associated-melanomas using targeted single-cell RNA-sequencing (n=12) enabled us to reconstruct the cellular trajectories from the premalignant to the malignant melanocyte state.Additionally, we performed untargeted spatial transcriptomics on two primary human melanoma, at a resolution of 0.5 m (Open-ST [2]), to study the behavior of tumor cells and their interactions with neighboring immune and stromal cells at a subcellular resolution.Results: We detected a population of nevus melanocytes characterized by PYGL and PCDH7 expression whereas the melanoma populations lossed the nevus-associated potential tumor suppressor genes ARRDC3 and CRTAC1.By performing spatially-constrained receptor-ligand interaction analysis we identified signaling hubs that potentially drive cancer progression.Conclusions: In summary, we performed high-throughput, single-cell and spatial transcriptomic analyses of primary human melanoma to gain deeper understanding of the tumor initiation and malignant transformation.