Dysplastic nevi and melanoma: microRNAs tell a divergent story

Background: dysplastic nevi (DN) share some clinical and histological features with melanoma and have been considered intermediate lesions toward malignant transformation. However, scientific evidence of DN representing melanoma precursors is still incomplete, and many observations pointed toward their being a distinct biological entity. The current definition of DN is also confusing and the practical consequence of this uncertainty is the excessive excision of DN with severe atypia. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and whose global expression can classify normal and pathological tissues. Objectives: given these considerations, we decided to perform a small RNA profiling study in a group of DN and invasive melanomas obtained from the same patient, to assess tumor evolution according to the global microRNA expression. Methods: we performed a small-RNA sequencing of 6 DN, 2 congenital nevi and 4 cutaneous melanomas obtained from 4 subjects and evaluated the global miRNA expression correlation between samples. Results and conclusions: the hierarchical clustering and principal component analyses of global miRNA expression, independently grouped together DN and their matching congenital nevi and showed a divergence of DN miRNA profile from melanoma. Our study suggests that DN have a peculiar and different miRNA expression profile compared to melanomas developed in the same patient, thus supporting the hypothesis that DN are distinct biological entities and not melanoma precursors.