The p.V600E mutation in the BRAF gene (BRAF^V600E ) is the most frequent mutation in cutaneous melanoma and is a recurrent alteration found in common benign naevi. The analysis of cell-free BRAF^V600E mutation (cfBRAF^V600E ) in plasma has emerged as a biomarker for monitoring prognosis and treatment response in melanoma patients.

To quantify cfBRAF^V600E levels in plasma from melanoma patients and from patients without melanoma having regular follow-up of their melanocytic lesions, in order to assess the clinical significance of the test.

We quantified cfBRAF^V600E by droplet digital PCR in plasma from 146 patients without melanoma undergoing continuous dermatological screening, 26 stage III and 7 stage IV patients with BRAF-mutant melanoma, and 32 melanoma patients free of disease for 3 or more years.

Among disease-free patients and non-melanoma individuals, 52% presented a high naevus count (>50) and 49% had clinically atypical naevi. cfBRAF^V600E was detected in 71·4% of stage IV and 15·4% of stage III melanoma patients and in 1·4% of non-melanoma individuals. No cfBRAF^V600E was detected in disease-free melanoma patients. Non-melanoma individuals had lower cfBRAF^V600E levels compared to melanoma patients. We established a variant allelic frequency of 0·26% or five cfBRAF^V600E copies/mL as the optimal cut-off value for identifying melanoma patients with >99% of specificity.

The study suggests that naevus related factors do not influence the detection of cfBRAF^V600E in non-melanoma individuals, and support the clinical diagnostic value of plasma cfBRAF^V600E quantification in melanoma patients. This article is protected by copyright. All rights reserved.