The NF1 gene in tumor syndromes and melanoma

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 a...

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Bibliographic Details
Published in:Laboratory investigation 2017-02, Vol.97 (2), p.146-157
Main Authors: Kiuru, Maija, Busam, Klaus J
Format: Article
Language:English
Subjects:
631/67/1813
692/420/755
Genetic Predisposition to Disease - genetics
Humans
Laboratory Medicine
Medicine
Medicine & Public Health
Melanoma - genetics
Melanoma - pathology
Models, Genetic
Mutation
Neurofibromatosis 1 - genetics
Neurofibromatosis 1 - pathology
Neurofibromin 1 - genetics
pathobiology-in-focus
Pathology
Signal Transduction - genetics
Skin Neoplasms - genetics
Skin Neoplasms - pathology
Syndrome
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Summary: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.
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.2016.142