Spitz nevi and Spitzoid melanomas - Exome sequencing and comparison to conventional melanocytic nevi and melanomas

摘要

We performed exome-sequencing of 77 melanocytic specimens composed of Spitz nevi (n=29), Spitzoid melanomas (n=27) and benign melanocytic nevi (n=21), and compared the results to published melanoma sequencing data. Our study highlights the prominent similarity between Spitzoid and conventional melanomas with similar copy number changes and high and equal numbers of ultraviolet-induced coding mutations affecting similar driver genes. Mutations in MEN1, PRKAR1A, and DNMT3A in Spitzoid melanomas may indicate involvement of the protein kinase-A pathway, or a role of DNA methylation in the disease. In addition to activating HRAS variants, there were few mutations in Spitz nevi, and few copy number changes other than 11p amplification and chromosome 9 deletions. Similarly, there were no large-scale copy number alterations and few somatic alterations other than activating BRAF or NRAS mutations in conventional nevi. A presumed melanoma driver mutation (IDH1^Arg132Cys) was revealed in one of the benign nevi. In conclusion, our exome data show significantly lower somatic mutation burden in both Spitz and conventional nevi compared to their malignant counterparts, and high genetic similarity between Spitzoid and conventional melanoma.