Oncogenic codon 13 NRAS mutation in a primary mesenchymal brain neoplasm and nevus of a child with neurocutaneous melanosis

被引：19
作者：
Shih F. [1 ]
Yip S. [2 ]
McDonald P.J. [3 ]
Chudley A.E. [4 ]
Del Bigio M.R. [5 ]
机构：
[1] Diagnostic Services Manitoba, Winnipeg, MB
[2] University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, BC
[3] University of Manitoba, Section of Neurosurgery, Winnipeg, MB
[4] University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB
[5] University of Manitoba and Diagnostic Services Manitoba, Department of Pathology, Brodie Centre, Winnipeg, R3E 3P5, MB
来源：
Acta Neuropathologica Communications | / 2卷 / 1期
关键词：
Brain tumor; Genetic mutation; Melanosis; Somatic mosaicism;
D O I：
10.1186/s40478-014-0140-8
中图分类号：
学科分类号：
摘要：
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. © 2014 Shih et al.; licensee BioMed Central Ltd.
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