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GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma

Several tumors, including uveal melanoma, show somatic mutations of GNAQ/GNA11. Circumscribed choroidal hemangioma is a benign tumor that becomes symptomatic in adulthood. In some patients, morphologic examination of biopsies is required for differential diagnosis between amelanotic choroidal melano...

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Autores principales: Le Guin, Claudia Helga Dorothee, Metz, Klaus Alfred, Kreis, Stefan Horst, Bechrakis, Nikolaos Emmanouel, Bornfeld, Norbert, Zeschnigk, Michael, Lohmann, Dietmar Rudolf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679048/
https://www.ncbi.nlm.nih.gov/pubmed/31336681
http://dx.doi.org/10.3390/cancers11071031
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author Le Guin, Claudia Helga Dorothee
Metz, Klaus Alfred
Kreis, Stefan Horst
Bechrakis, Nikolaos Emmanouel
Bornfeld, Norbert
Zeschnigk, Michael
Lohmann, Dietmar Rudolf
author_facet Le Guin, Claudia Helga Dorothee
Metz, Klaus Alfred
Kreis, Stefan Horst
Bechrakis, Nikolaos Emmanouel
Bornfeld, Norbert
Zeschnigk, Michael
Lohmann, Dietmar Rudolf
author_sort Le Guin, Claudia Helga Dorothee
collection PubMed
description Several tumors, including uveal melanoma, show somatic mutations of GNAQ/GNA11. Circumscribed choroidal hemangioma is a benign tumor that becomes symptomatic in adulthood. In some patients, morphologic examination of biopsies is required for differential diagnosis between amelanotic choroidal melanoma and circumscribed choroidal hemangioma. Here, we report the results of GNAQ/GNA11 mutation analysis in samples from circumscribed choroidal hemangioma. Deep amplicon sequencing (Illumina MiSeq, San Diego, CA, USA) of positions R183 and Q209 of GNAQ and GNA11 in tissue samples from 33 patients with histologically diagnosed circumscribed choroidal hemangioma. All patients underwent biopsy or enucleation at our clinic between 2008 and 2018. To enable detection of variant alleles at low fractions, read depth exceeded 15,000-fold. DNA for genetic analysis was prepared from either snap-frozen (n = 22) or FFPE (n = 11) tissue samples. Samples from 28/33 patients (85%) showed a somatic missense mutation of GNAQ (c.626 A > G) predicted to result in p.Q209R. Variant allele fraction was variable (range 2.3% to 28%). Variants of GNAQ resulting in p.Q209 are characteristic for circumscribed choroidal hemangiomas. It appears that the GNAQ mutation spectrum in this tumor is narrow, possibly restricted to p.Q209R. Moreover, the spectrum is distinct from that of uveal melanoma, in which alterations resulting in p.Q209R are very rare.
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spelling pubmed-66790482019-08-19 GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma Le Guin, Claudia Helga Dorothee Metz, Klaus Alfred Kreis, Stefan Horst Bechrakis, Nikolaos Emmanouel Bornfeld, Norbert Zeschnigk, Michael Lohmann, Dietmar Rudolf Cancers (Basel) Article Several tumors, including uveal melanoma, show somatic mutations of GNAQ/GNA11. Circumscribed choroidal hemangioma is a benign tumor that becomes symptomatic in adulthood. In some patients, morphologic examination of biopsies is required for differential diagnosis between amelanotic choroidal melanoma and circumscribed choroidal hemangioma. Here, we report the results of GNAQ/GNA11 mutation analysis in samples from circumscribed choroidal hemangioma. Deep amplicon sequencing (Illumina MiSeq, San Diego, CA, USA) of positions R183 and Q209 of GNAQ and GNA11 in tissue samples from 33 patients with histologically diagnosed circumscribed choroidal hemangioma. All patients underwent biopsy or enucleation at our clinic between 2008 and 2018. To enable detection of variant alleles at low fractions, read depth exceeded 15,000-fold. DNA for genetic analysis was prepared from either snap-frozen (n = 22) or FFPE (n = 11) tissue samples. Samples from 28/33 patients (85%) showed a somatic missense mutation of GNAQ (c.626 A > G) predicted to result in p.Q209R. Variant allele fraction was variable (range 2.3% to 28%). Variants of GNAQ resulting in p.Q209 are characteristic for circumscribed choroidal hemangiomas. It appears that the GNAQ mutation spectrum in this tumor is narrow, possibly restricted to p.Q209R. Moreover, the spectrum is distinct from that of uveal melanoma, in which alterations resulting in p.Q209R are very rare. MDPI 2019-07-22 /pmc/articles/PMC6679048/ /pubmed/31336681 http://dx.doi.org/10.3390/cancers11071031 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Le Guin, Claudia Helga Dorothee
Metz, Klaus Alfred
Kreis, Stefan Horst
Bechrakis, Nikolaos Emmanouel
Bornfeld, Norbert
Zeschnigk, Michael
Lohmann, Dietmar Rudolf
GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma
title GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma
title_full GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma
title_fullStr GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma
title_full_unstemmed GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma
title_short GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma
title_sort gnaq q209r mutations are highly specific for circumscribed choroidal hemangioma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679048/
https://www.ncbi.nlm.nih.gov/pubmed/31336681
http://dx.doi.org/10.3390/cancers11071031
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