Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system

• DOI: 10.1007/s00401-009-0611-3
• Publication Date: 2009-11-21T01:12:27Z
• Authors: Heidi V. N. Küste...; Annelies Klaasen; Benno Küsters; Patricia J. T. A....; Ilse A. C. H. van...; Marcory R. C. F. ...; Guido Reifenberger; Pieter Wesseling; Willeke A. M. Blokx
• Keywords: GNAQ; HRAS

Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon derived from melanocytes that normally can be found in leptomeninges. They cover a spectrum malignancy grades ranging low-grade melanocytomas to lesions intermediate and overtly malignant melanomas. Characteristic genetic alterations this group have not yet been identified. Using direct sequencing, we investigated 19 primary CNS (12 melanocytomas, 3 intermediate-grade 4 melanomas) for hotspot oncogenic mutations commonly tumors skin (BRAF, NRAS, HRAS genes) uvea (GNAQ gene). Somatic GNAQ gene at codon 209, resulting constitutive activation GNAQ, were detected 7/19 (37%) tumors, including 6/12 0/3 1/4 These GNAQ-mutated predominantly located around spinal cord (6/7). One melanoma carried BRAF point mutation is frequently cutaneous melanomas (c.1799 T>A, p.V600E), raising question whether metastatic rather than tumor. No or NRAS detected. We conclude somatic 209 frequent event CNS. This finding provides new insight pathogenesis these suggests GNAQ-dependent mitogen-activated kinase signaling promising therapeutic target tumors. The prognostic predictive value needs determined future studies.