NRAS^Q61K/R/L Mutant Allele Frequency in Melanoma and its Correlation With Clinicopathological Characteristics

Background/Aim: 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^Q61R/K/L as a possible prognostic biomarker, expanding the classical histopathological prognostic criteria.

Materials and Methods: Twenty-six NRAS^Q61R/K/L mutated melanomas were analysed using next generation sequencing, to assess the possible correlation between MAF and clinicopathological characteristics.

Results: 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.

Conclusion: 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.