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

Küsters‐Vandevelde, Heidi V.N.; Klaasen, Annelies; Küsters, Benno; Groenen, Patricia J.T.A.; Grunsven, Ilse A. C. H. van Engen-van; Dijk, Marcory R. C. F. van; Reifenberger, Guido; Wesseling, Pieter; Blokx, Willeke A.M.

doi:10.1007/s00401-009-0611-3

Cited by 129 publications

(118 citation statements)

References 30 publications

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“…They have been revealed in a number of melanocytic neoplasms, including 83% of all uveal melanomas (including 22% of the iris melanomas), 90% of the uveal melanoma metastases, choroidal nevi, blue nevi (skin and oral cavity), oculodermal melanocytosis, and central nervous system and ciliochoroidal melanocytomas [3,12,13,14,15,16,17,18,19] (table 2). The present study indicates that ophthalmic melanocytomas of the iridociliary body and optic nerve can be added to this list.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Somatic GNAQ, GNA11, BAP1 and SF3B1 Mutations in Ophthalmic Melanocytomas

et al. 2016

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Purpose: The aim of this study was to use massively parallel DNA sequencing to identify GNAQ/11, BAP1 and SF3B1 mutations in ophthalmic melanocytoma. Procedures: Six ophthalmic melanocytoma specimens (1 iridociliary and 5 optic nerve) were profiled for genomic alterations in GNAQ/11, BAP1 and SF3B1 using a custom deep sequencing assay. This assay uses solution phase hybridization-based exon capture and deep-coverage massively parallel DNA sequencing to interrogate all protein-coding exons and select introns. Results: The only iridociliary melanocytoma showed a mutation in GNAQ but not in BAP1. Of the 2 optic-nerve melanocytomas that developed into melanoma, one had a GNAQ mutation and both a BAP1 mutation and monosomy 3. The remaining 3 optic-nerve melanocytomas did not reveal mutations in GNAQ/11 or BAP1. SF3B1 mutations were not detected in any specimen. Conclusions: The presence of GNAQ mutation in some iridociliary and optic-nerve melanocytomas suggests a possible relationship between ophthalmic melanocytoma and other ophthalmic melanocytic neoplasms. BAP1 mutation may accompany the transformation of ophthalmic melanocytoma to melanoma.

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Section: Discussionmentioning

confidence: 99%

Investigation of Somatic GNAQ, GNA11, BAP1 and SF3B1 Mutations in Ophthalmic Melanocytomas

et al. 2016

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“…Less frequently, melanomas contain KIT mutations, particularly mucosal melanoma or melanomas arising on acral or on sun-damaged sites [53]. GNAQ and GNA11 mutations were discovered in uveal and CNS melanomas, defining additional molecular melanoma subgroups [81,129,200]. Frequently, melanomas also contain PTEN, CDKN2A, CDK4, and CCND1 copy number alterations that help to define molecular subgroups [54,55].…”

Section: Somatic Genetic Factors: Tumor Subtypesmentioning

confidence: 99%

Melanoma Epidemiology and Prevention

et al. 2015

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The epidemiology of melanoma is complex, and individual risk depends on sun exposure, host factors, and genetic factors, and in their interactions as well. Sun exposure can be classified as intermittent, chronic, or cumulative (overall) exposure, and each appears to have a different effect on type of melanoma. Other environmental factors, such as chemical exposures-either through occupation, atmosphere, or food-may increase risk for melanoma, and this area warrants further study. Host factors that are well known to be important are the numbers and types of nevi and the skin phenotype. Genetic factors are classified as

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“…14 Küsters-Vandevelde et al 7 suggested that the presence of a GNAQ mutation and the absence of typical mutations of cutaneous melanomas such as BRAF or NRAS in a melanocytic neoplasm of the CNS strongly indicate a primary CNS tumor. On the other hand, the presence of a BRAF and NRAS mutation in the absence of a GNAQ mutation points to a primary cutaneous melanoma.…”

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confidence: 99%

The GNAQ in the haystack: intramedullary meningeal melanocytoma of intermediate grade at T9–10 in a 58-year-old woman

Hoffmann

Koelsche²,

Seiz-Rosenhagen³

et al. 2016

JNS

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M eningeal melanocytomas are extremely rare tumors originating from leptomeningeal melanocytes. The first reported description, in the early 1970s, was by Limas and Tio.10 Although little is known about this tumor entity as only a few case reports have been published over the past few decades, the tumors mostly occur along the spine and the posterior fossa with a peak incidence around the 5th decade and a slight female predominance. 3,11 According to the classification suggested by Brat et al., 2 melanocytic neoplasms are categorized histologically as melanocytomas, melanocytomas of intermediate grade, or melanomas exhibiting typical malignant features such as necrosis and high mitotic activity. Recent in-depth molecular characterization of melanocytomas revealed distinct mutational and chromosomal fingerprints separating melanocytomas from other melanotic tumors such as melanoma metastases or melanotic schwannomas. 6Treatment aims at the complete surgical removal of the tumor and postoperative adjuvant radiotherapy. case reportA 58-year-old woman presented with a history of progressive ataxia, progressive urinary and bowel incontinence, and weight loss of 6 kg over a period of 6-8 weeks. Neurological examination revealed a paraparesis of the lower extremities (M0/5 muscle strength grade of the right leg; M1-2/5, left leg) with paresthesia and hypesthesia starting from the T-10 dermatome downward.Her medical history included breast cancer diagnosed in 2008, which was treated with a lumpectomy, adjuvant chemotherapy (6 cycles of Taxotere, Adriamycin, and cyclophosphamide), and postoperative whole breast radiotherapy (including supraclavicular lymph nodes) with a total dose of 50.4 Gy and followed by a 16-Gy boost to the tumor bed.Upon admission, MRI of the spine revealed a 3.7-cm isodense/slightly hyperintense intramedullary lesion at T9-10. After administration of gadolinium, the lesion appeared hyperintense on T1-weighted images (Fig. 1A). T2-weighted images showed a myelopathy signal from T-7 to T-12. The differential diagnosis included ependymoma, astrocytoma, and intraspinal metastasis.The patient thus underwent a laminectomy at the T9-10 levels and a complete microsurgical resection of the intramedullary tumor under continuous neuromonitoring. The lesion was grayish-red and heavily vascularized with a macroscopic appearance that closely resembled an epen- Meningeal melanocytomas are rare tumors. They are derived from leptomeningeal melanocytes and predominantly occur along the spine and the posterior fossa. Here, the authors report a case of intramedullary melanocytoma of intermediate grade in a 58-year-old female patient who was initially misdiagnosed with malignant melanoma until mutational analyses of a panel of genes associated with melanotic tumors led to reclassification.

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

Cited by 129 publications

References 30 publications

Investigation of Somatic <b><i>GNAQ, GNA11, BAP1</i></b> and <b><i>SF3B1</i></b> Mutations in Ophthalmic Melanocytomas

Investigation of Somatic <b><i>GNAQ, GNA11, BAP1</i></b> and <b><i>SF3B1</i></b> Mutations in Ophthalmic Melanocytomas

Melanoma Epidemiology and Prevention

The GNAQ in the haystack: intramedullary meningeal melanocytoma of intermediate grade at T9–10 in a 58-year-old woman

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