The presence of either a predominantly dermal growth pattern or large junctional nests was found in 13 of 15 naevi positive for BRAFV600E and in two of 10 naevinegative forBRAFV600E (86·7% vs. 20%, P = 0·002).
Focused amplicon deep sequencing on DNA extracted from the brain tumor and a cutaneous nevus revealed a heterozygous (c.37G>C; p.G13R) substitution in the NRAS gene.
Biopsy findings from 1 unchanged and 1 involuted nevus showed BRAF wild type in the unchanged nevus, BRAFV600E mutation in the involuting nevus, and no malignant histopathologic characteristics in either one.
Mutations of the BRAF gene are correlated with younger age, a higher number of melanocytic naevi and a tumour location in intermittently UV-exposed skin.
We found BRAF(V600E) mutations in the melanocytic nevi to be fully clonal, strongly suggesting that BRAF-activating mutations typically are early initiating events in melanocytic neoplasia.
BRAF(V600E) mutations are also present in benign melanocytic naevi, highlighting the importance of additional genetic alterations in the genesis of malignant tumours.
Oncogenic BRAF mutation had been considered to be a founder event in the formation of melanocytic tumours; however, we recently argued against this notion by showing marked polyclonality of BRAF mutations in acquired melanocytic nevi (Lin et al, J Natl Cancer Inst., 2009; 101:1423-7).
Both Spitz naevi and spitzoid melanoma had a lower combined BRAF and NRAS mutation frequency compared with common acquired naevi (P = 0.0001) and common forms of melanoma (P = 0.0072), respectively.
Both Spitz naevi and spitzoid melanoma had a lower combined BRAF and NRAS mutation frequency compared with common acquired naevi (P = 0.0001) and common forms of melanoma (P = 0.0072), respectively.
The polyclonality of BRAF mutations in acquired melanocytic nevi suggests that mutation of BRAF may not be an initial event in melanocyte transformation.
Our results suggest that although nevus propensity is important for the occurrence of both BRAF and NRAS-mutant melanomas, ambient UV irradiance influences risk differently based on the age of exposure.