Biology and genetics of acquired and congenital melanocytic naevi

Maher NG, Scolyer RA, Colebatch AJ Pathology, 2022, ISSN 0031-3025


Acquired and congenital melanocytic naevi are common benign neoplasms. Understanding their biology and genetics will help clinicians and pathologists correctly diagnose melanocytic tumours, and generate insights into naevus aetiology and melanomagenesis.
Genomic data from published studies analysing acquired and congenital melanocytic naevi, including oncogenic driver mutations, common melanoma associated mutations, copy number aberrations, somatic mutation signature patterns, methylation profile, and single nucleotide polymorphisms, were reviewed. Correlation of genomic changes to dermoscopic features, particular anatomic sites and total body naevus counts, was also performed. This review also highlights current scientific theories and evidence concerning naevi growth arrest.

Acquired and congenital melanocytic naevi show simple genomes, typically characterised by mutually exclusive single oncogenic driver mutations in either BRAF or NRAS genes. Genomic differences exist between acquired and congenital naevi, common and dysplastic naevi, and by dermoscopic features. Acquired naevi show a higher rate of BRAF hotspot mutations and a lower rate of NRAS hotspot mutations compared to congenital naevi. Dysplastic naevi show upregulation of follicular keratinocyte-related genes compared to common naevi. Anatomical locations and DNA signatures of naevi implicates ultraviolet radiation and non-ultraviolet radiation pathways in naevogenesis.

DNA driver point mutations in acquired and congenital melanocytic naevi have been well characterised. Future research is required to better understand transcriptional and epigenetic changes in naevi, as well as those regulating naevus growth arrest and cell environment signalling.