NRAS Mutant Allele Frequency in Melanoma and its Correlation With Clinicopathological Characteristics

Approximately 80% of NRAS mutations in melanoma occur at codon 61, locking the NRAS protein into a GTP-bound state.We aimed to evaluate the mutant allele frequency (MAF) of NRAS as a possible prognostic biomarker, expanding the classical histopathological prognostic criteria.

Twenty-six NRAS mutated melanomas were analysed using next generation sequencing, to assess the possible correlation between MAF and clinicopathological characteristics.

A statistically significant difference (p-value <0.05) was found between the ratio of patients with MAF ≤30% (12/26, 46%) and MAF >30% (14/26, 54%). MAF ≤30% was more common in primary melanomas (10/12, 83.3%) and was also observed in patients with MAF >30%. Cases with MAF ≤30% had a higher percentage of Breslow's depth ≤1 mm (5/12, 41.7%) and a low Clark level (III) (6/12, 50%). Patients with MAF >30% and a high Clark level (V) showed a higher percentage (5/14, 57.2%). Nodular/epithelioid cell types were more frequently observed in MAF ≤30% (9/12, 75%) and MAF >30% (8/14, 57.2%) groups. A slightly higher number of MAF ≤30% cases were found with tumor cell percentages ranging from 11-40% (5/14, 41.7%), while MAF >30% cases were more common in patients with ≥71% tumor cells (9/14, 64.3%) and this difference was statistically significant.

The MAF of NRAS was highly heterogeneous but was found to correlate with the percentage of tumor cells. To corroborate these data, the evaluation of NRAS MAF in a larger cohort of melanomas is necessary and fundamental.