Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system
Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon neoplasms derived from melanocytes that normally can be found in the leptomeninges. They cover a spectrum of malignancy grades ranging from low-grade melanocytomas to lesions of intermediate malignancy and overtly maligna...
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Published in | Acta neuropathologica Vol. 119; no. 3; pp. 317 - 323 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer-Verlag
01.03.2010
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon neoplasms derived from melanocytes that normally can be found in the leptomeninges. They cover a spectrum of malignancy grades ranging from low-grade melanocytomas to lesions of intermediate malignancy and overtly malignant melanomas. Characteristic genetic alterations in this group of neoplasms have not yet been identified. Using direct sequencing, we investigated 19 primary melanocytic lesions of the CNS (12 melanocytomas, 3 intermediate-grade melanocytomas, and 4 melanomas) for hotspot oncogenic mutations commonly found in melanocytic tumors of the skin (
BRAF, NRAS,
and
HRAS
genes) and uvea (
GNAQ
gene). Somatic mutations in the
GNAQ
gene at codon 209, resulting in constitutive activation of
GNAQ,
were detected in 7/19 (37%) tumors, including 6/12 melanocytomas, 0/3 intermediate-grade melanocytomas, and 1/4 melanomas. These
GNAQ
-mutated tumors were predominantly located around the spinal cord (6/7). One melanoma carried a
BRAF
point mutation that is frequently found in cutaneous melanomas (c.1799 T>A, p.V600E), raising the question whether this is a metastatic rather than a primary tumor. No
HRAS
or
NRAS
mutations were detected. We conclude that somatic mutations in the
GNAQ
gene at codon 209 are a frequent event in primary melanocytic neoplasms of the CNS. This finding provides new insight in the pathogenesis of these lesions and suggests that
GNAQ
-dependent mitogen-activated kinase signaling is a promising therapeutic target in these tumors. The prognostic and predictive value of
GNAQ
mutations in primary melanocytic lesions of the CNS needs to be determined in future studies. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0001-6322 1432-0533 |
DOI: | 10.1007/s00401-009-0611-3 |