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Review
. 2017 Feb;97(2):146-157.
doi: 10.1038/labinvest.2016.142. Epub 2017 Jan 9.

The NF1 gene in tumor syndromes and melanoma

Maija Kiuru  1 , Klaus J Busam  2
Affiliations
Review

The NF1 gene in tumor syndromes and melanoma

Maija Kiuru et al. Lab Invest. 2017 Feb.

Abstract

Activation of the RAS/MAPK pathway is critical in melanoma. Melanoma can be grouped into four molecular subtypes based on their main genetic driver: BRAF-mutant, NRAS-mutant, NF1-mutant, and triple wild-type tumors. The NF1 protein, neurofibromin 1, negatively regulates RAS proteins through GTPase activity. Germline mutations in NF1 cause neurofibromatosis type I, a common genetic tumor syndrome caused by dysregulation of the RAS/MAPK pathway, ie, RASopathy. Melanomas with NF1 mutations typically occur on chronically sun-exposed skin or in older individuals, show a high mutation burden, and are wild-type for BRAF and NRAS. Additionally, NF1 mutations characterize certain clinicopathologic melanoma subtypes, specifically desmoplastic melanoma. This review discusses the current knowledge of the NF1 gene and neurofibromin 1 in neurofibromatosis type I and in melanoma.

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Figures

Figure 1
Figure 1
The RAS/MAPK pathway and RASopathies.
See this image and copyright information in PMC

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