Genetic profile of naïve untreated primary cutaneous melanomas with a negative sentinel lymph node

Sentinel lymph node (SLN) biopsy is typically offered to patients with primary cutaneous melanomas (PCMs) of ≥ 1 mm depth, but not all SLNs are positive using this cutoff. To ascertain whether positivity is genetically regulated, genetic analysis was performed using an augmented enrichment-based next-generation DNA and RNA sequencing assay in SLN-negative (Group 1, n = 8, mean depth 1.3 mm) and SLN-positive PCMs (controls, Group 2, n = 4, mean depth 1.4 mm). In Group 1, the mean number of mutations was 21 (range 3-48) with the most frequent mutations occurring in NF1 (75%) followed by TP53 (63%), CDKN2A and BRAF (38%), and NRAS (25%), while in Group 2, the ean number of mutations was 9.5 (range 5-18) with mutations in NRAS and BRAF being the most frequent (50%) followed by those in ATM, CDKN2A, CDKN2B, and NOTCH1 (25%). Increased frequency of NF1-inactivating mutations in Group 1 provides provocative early data that the presence of NF1 mutations might confer a less aggressive phenotype.