Heppt MV et al. – NRAS-mutant tumors are more aggressive, particularly in early stages of melanoma.

Methods

• The mutational status of BRAF (exon 15) and NRAS (exon 2 and 3) was determined in melanoma samples of 217 patients with pyrosequencing and Sanger sequencing.
• The genotypes were correlated with clinical outcomes and pathologic features of the primary tumors.

Results

• Mutations in BRAF and NRAS were identified in 40.1% and 24.4% of patients, respectively.
• Concurrent mutations in both genes were detected in 2.3% of the patients; the remaining 33.2% were wild type.
• BRAF mutations were significantly associated with younger age at first diagnosis and truncal localization of the culprit primary.
• NRAS-mutant melanoma patients showed a higher frequency of nodal relapse and development of metastatic disease.
• The time to loco-regional nodal relapse was shortest in NRAS-mutant melanoma.
• A NRAS mutation was an independent risk factor for disease progression in multivariate analysis (HR = 2.01).
• BRAF-mutant melanoma patients exhibited better overall and relative survival.
• Genotype was not a consistent risk factor, but positive sentinel lymph node status (HR = 2.65) and treatment with ICB in stage IV disease (HR = 0.17) were significant multivariate risk factors.