Comparison of mutation profiles in primary melanomas and corresponding nodal naevi using next-generation sequencing

Nodal naevi (NN) represent aggregates of melanocytes within peripheral lymph nodes. NN are relatively often found in patients with malignant melanoma (MM), and may mimic metastatic disease.

To study mutation profiles in MM and NN to find out whether NN descend from a primary MM.

Next-generation sequencing was performed on formalin-fixed paraffin-embedded tissue of 26 pairs of primary MM and corresponding NN detected by sentinel lymph node biopsy, and 29 MM-characteristic genes were investigated.

In this study, 90% of mutations were detected exclusively in either MM or NN, but not both, in the same patient; the percentage of identical NN and MM mutations in the same individual was only 10%. The most frequently discovered shared mutations were a C>G substitution in the CDKN2A gene and in-frame deletion in ARID1A. Oncogenic driver mutations were frequently observed in MM but only rarely in NN. About three-quarters of mutations in both MM and NN were characterized by C>T or G>A substitutions. The detected rate of ultraviolet (UV)-related C>T base changes was comparably high in both primary MM (35%) and NN (32%).

Based on our data, it seems that NN descend from previously UV-exposed BRAF wildtype cutaneous melanocytes, rather than from primary MM or arrested progenitor cells.