title: Oncogenic codon 13 NRAS mutation in a primary mesenchymal brain neoplasm and nevus of a child with neurocutaneous melanosis.
abstract: A 28-month female with a clinical diagnosis of neurocutaneous melanosis and numerous intracranial abnormalities (including a right choroid plexus tumor and left hemimegalencephaly) presented with a rapidly expanding tumor in the left occipital cerebrum. Microscopic examination of the resected specimen revealed a myxoid mesenchymal neoplasm consisting of fusiform cells that were immunoreactive for vimentin, CD34, and P53 but no melanocyte markers. Focused amplicon deep sequencing on DNA extracted from the brain tumor and a cutaneous nevus revealed a heterozygous (c.37G>C; p.G13R) substitution in the NRAS gene. DNA sequencing of "normal" skin and buccal swab showed the identical NRAS change albeit at lower allelic frequency. Her parents did not harbor the NRAS mutation. The skin lesion, but not the brain tumor, had a BRAF mutation (c.1397G>T; p.G466V). A germline single nucleotide polymorphism in MET was found in the child and her father (c.3209C>T; p.T1010I). The findings suggest NRAS mosaicism that occurred sometime after conception and imply an oncogenic role of the activating NRAS mutation in both the brain and skin lesions in this child.
authors.forename: Francis
authors.initials: F
authors.lastname: Shih
authors.forename: Stephen
authors.initials: S
authors.lastname: Yip
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McDonald
authors.forename: Albert E
authors.initials: AE
authors.lastname: Chudley
authors.forename: Marc R
authors.initials: MR
authors.lastname: Del Bigio
mesh_terms: D018952:Antigens, CD34 / Q000235:genetics; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics*; D002675:Child, Preschool; D016545:Choroid Plexus Neoplasms / Q000235:genetics*; D003062:Codon; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008548:Melanosis / Q000150:complications / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D018396:Mucin-1 / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D020752:Neurocutaneous Syndromes / Q000150:complications / Q000235:genetics*; D012878:Skin Neoplasms / Q000150:complications / Q000235:genetics*; D016159:Tumor Suppressor Protein p53; D014746:Vimentin / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D003062:Codon; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D018396:Mucin-1; D016159:Tumor Suppressor Protein p53; D014746:Vimentin; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human