Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS
- PMID: 23392294
- PMCID: PMC3678977
- DOI: 10.1038/jid.2013.70
Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS
Erratum in
-
Erratum.J Invest Dermatol. 2016 Nov;136(11):2326. doi: 10.1016/j.jid.2016.09.009. J Invest Dermatol. 2016. PMID: 27772549 No abstract available.
Abstract
Congenital melanocytic nevi (CMN) can be associated with neurological abnormalities and an increased risk of melanoma. Mutations in NRAS, BRAF, and Tp53 have been described in individual CMN samples; however, their role in the pathogenesis of multiple CMN within the same subject and development of associated features has not been clear. We hypothesized that a single postzygotic mutation in NRAS could be responsible for multiple CMN in the same individual, as well as for melanocytic and nonmelanocytic central nervous system (CNS) lesions. From 15 patients, 55 samples with multiple CMN were sequenced after site-directed mutagenesis and enzymatic digestion of the wild-type allele. Oncogenic missense mutations in codon 61 of NRAS were found in affected neurological and cutaneous tissues of 12 out of 15 patients, but were absent from unaffected tissues and blood, consistent with NRAS mutation mosaicism. In 10 patients, the mutation was consistently c.181C>A, p.Q61K, and in 2 patients c.182A>G, p.Q61R. All 11 non-melanocytic and melanocytic CNS samples from 5 patients were mutation positive, despite NRAS rarely being reported as mutated in CNS tumors. Loss of heterozygosity was associated with the onset of melanoma in two cases, implying a multistep progression to malignancy. These results suggest that single postzygotic NRAS mutations are responsible for multiple CMN and associated neurological lesions in the majority of cases.
Figures
Comment in
-
Making a mountain out of a molehill: NRAS, mosaicism, and large congenital nevi.J Invest Dermatol. 2013 Sep;133(9):2127-30. doi: 10.1038/jid.2013.146. J Invest Dermatol. 2013. PMID: 23949765
Similar articles
-
Making a mountain out of a molehill: NRAS, mosaicism, and large congenital nevi.J Invest Dermatol. 2013 Sep;133(9):2127-30. doi: 10.1038/jid.2013.146. J Invest Dermatol. 2013. PMID: 23949765
-
BRAF mutations are also associated with neurocutaneous melanocytosis and large/giant congenital melanocytic nevi.Pediatr Dev Pathol. 2015 Jan-Feb;18(1):1-9. doi: 10.2350/14-10-1566-OA.1. Epub 2014 Dec 9. Pediatr Dev Pathol. 2015. PMID: 25490715
-
Genetic Abnormalities in Large to Giant Congenital Nevi: Beyond NRAS Mutations.J Invest Dermatol. 2019 Apr;139(4):900-908. doi: 10.1016/j.jid.2018.07.045. Epub 2018 Oct 22. J Invest Dermatol. 2019. PMID: 30359577
-
Congenital melanocytic nevi: where are we now? Part I. Clinical presentation, epidemiology, pathogenesis, histology, malignant transformation, and neurocutaneous melanosis.J Am Acad Dermatol. 2012 Oct;67(4):495.e1-17; quiz 512-4. doi: 10.1016/j.jaad.2012.06.023. J Am Acad Dermatol. 2012. PMID: 22980258 Review.
-
Congenital melanocytic nevi.Curr Opin Pediatr. 2020 Aug;32(4):491-497. doi: 10.1097/MOP.0000000000000924. Curr Opin Pediatr. 2020. PMID: 32692047 Review.
Cited by
-
The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact.Fluids Barriers CNS. 2024 Mar 4;21(1):24. doi: 10.1186/s12987-024-00513-z. Fluids Barriers CNS. 2024. PMID: 38439105 Free PMC article. Review.
-
Missense mutation of NRAS is associated with malignant progression in neurocutaneous melanosis.Acta Neuropathol Commun. 2024 Jan 22;12(1):14. doi: 10.1186/s40478-024-01723-0. Acta Neuropathol Commun. 2024. PMID: 38254245 Free PMC article.
-
Piecing together the mosaic of rare skin diseases: an interview with Veronica Kinsler.Dis Model Mech. 2024 Jun 1;17(6):dmm050636. doi: 10.1242/dmm.050636. Epub 2024 Jan 18. Dis Model Mech. 2024. PMID: 38235593 Free PMC article. No abstract available.
-
Incidence of neurocutaneous melanosis in Japanese pediatric patients with congenital melanocytic nevi.Sci Rep. 2023 Sep 30;13(1):16442. doi: 10.1038/s41598-023-43829-w. Sci Rep. 2023. PMID: 37777590 Free PMC article.
-
Advancing Cancer Research: Current Knowledge on Cutaneous Neoplasia.Int J Mol Sci. 2023 Jul 6;24(13):11176. doi: 10.3390/ijms241311176. Int J Mol Sci. 2023. PMID: 37446352 Free PMC article. Review.
References
-
- Agero AL, Benvenuto-Andrade C, Dusza SW, et al. Asymptomatic neurocutaneous melanocytosis in patients with large congenital melanocytic nevi: a study of cases from an Internet-based registry. J Am Acad Dermatol. 2005;53:959–965. - PubMed
-
- Amir J, Metzker A, Nitzan M. Giant pigmented nevus occurring in one identical twin. Arch Dermatol. 1982;118:188–189. - PubMed
-
- Bauer J, Curtin JA, Pinkel D, et al. Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol. 2007;127:179–182. - PubMed
Publication types
MeSH terms
Substances
Supplementary concepts
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous