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http://purl.uniprot.org/citations/23303902http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23303902http://www.w3.org/2000/01/rdf-schema#comment"

Unlabelled

NRAS mutations are common in human melanoma. To produce a mouse model of NRAS-driven melanoma, we expressed oncogenic NRAS (NRAS(G12D)) in mouse melanocytes. When NRAS(G12D) was expressed in the melanocytes of developing embryos, it induced melanocyte proliferation and congenital melanocytic lesions reminiscent of human blue nevi but did not induce cutaneous melanoma. Unexpectedly, however, it did induce early-onset primary melanoma of the central nervous system (CNS). The tumors were rapidly proliferating and caused neurologic symptoms, rapid health deterioration, and death. NRAS is not a common driver oncogene of primary melanoma of the CNS in adults, but we report two cases of primary melanoma of the CNS in children, both of which carried oncogenic mutations in NRAS. We conclude that acquisition of somatic mutations in NRAS in CNS melanocytes is a predisposing risk factor for primary melanoma of the CNS in children, and we present a mouse model of this disease.

Significance

We show that the acquisition of NRAS mutations in melanocytes during embryogenesis is a risk factor for early-onset melanoma of the CNS. We have developed a powerful mouse model to study this rare but devastating childhood disease, and to develop therapeutic approaches for its treatment."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.org/dc/terms/identifier"doi:10.1158/2159-8290.cd-12-0464"xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Renier W."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Pedersen M."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Marais R."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Schieving J."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Groenen P.J.T.A."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Kusters B."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Wesseling P."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Springer C.J."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Niculescu-Duvaz I."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Viros A."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Blokx W.A.M."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Kusters-Vandevelde H.V.N."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"van Engen-van Grunsven I.A."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Sanchez-Laorden B."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/author"Gilhuis J.H."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/name"Cancer Discov"xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/pages"458-469"xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/title"Primary melanoma of the CNS in children is driven by congenital expression of oncogenic NRAS in melanocytes."xsd:string
http://purl.uniprot.org/citations/23303902http://purl.uniprot.org/core/volume"3"xsd:string
http://purl.uniprot.org/citations/23303902http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23303902
http://purl.uniprot.org/citations/23303902http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23303902