GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas

Jasmine H. Francis, Tatyana Milman, Hans Grossniklaus, Daniel Albert, Robert Folberg, Gregory Levitin, Sarah Coupland, Federica Catalanotti, David Rabady, Cyriac Kandoth, Klaus Busam, David Abramson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: GNAQ mutations have been identified in port wine stains (both syndromic and nonsyndromic) and melanocytic ocular neoplasms. This study investigates the presence of GNAQ mutations in diffuse (those associated with Sturge–Weber syndrome [SWS]) and solitary choroidal hemangiomas. Participants: Tissue from 11 patients with the following diagnoses: port wine stain (n = 3), diffuse choroidal hemangioma (n = 1), solitary choroidal hemangioma (n = 6), and choroidal nevus (n = 1). Methods: Ten specimens were interrogated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, a hybridization capture-based next-generation sequencing assay for targeted deep sequencing of all exons and selected introns of 468 key cancer genes in formalin-fixed, paraffin-embedded tumors. Digital polymerase chain reaction was used to detect GNAQ Q209 mutation in 1 specimen. Main Outcome Measures: Detection of GNAQ codon-specific mutation. Results: Activating somatic GNAQ mutations (c.547C > T; p.Arg183Cys) were found in 100% (3 of 3) of the port wine stain and in the diffuse choroidal hemangioma. Somatic GNAQ mutations (c.626A > T; p.Gln209Leu) were found in 100% (6 of 6) of the solitary choroidal hemangiomas and (c.626A > C; p.Gln209Pro) in the choroidal nevus. Conclusions: GNAQ mutations occur in both diffuse and solitary hemangiomas, although at distinct codons. An R183 codon is mutant in diffuse choroidal hemangiomas, consistent with other Sturge–Weber vascular malformations. By contrast, solitary choroidal hemangiomas have mutations in the Q209 codon, similar to other intraocular melanocytic neoplasms.

Original languageEnglish (US)
JournalOphthalmology
DOIs
StateAccepted/In press - Jan 1 2019
Externally publishedYes

Fingerprint

Hemangioma
Mutation
Port-Wine Stain
Codon
Nevus
Eye Neoplasms
High-Throughput Nucleotide Sequencing
Neoplasms
Vascular Malformations
Neoplasm Genes
Paraffin
Introns
Formaldehyde
Exons
Outcome Assessment (Health Care)
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Francis, J. H., Milman, T., Grossniklaus, H., Albert, D., Folberg, R., Levitin, G., ... Abramson, D. (Accepted/In press). GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas. Ophthalmology. https://doi.org/10.1016/j.ophtha.2018.12.011

GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas. / Francis, Jasmine H.; Milman, Tatyana; Grossniklaus, Hans; Albert, Daniel; Folberg, Robert; Levitin, Gregory; Coupland, Sarah; Catalanotti, Federica; Rabady, David; Kandoth, Cyriac; Busam, Klaus; Abramson, David.

In: Ophthalmology, 01.01.2019.

Research output: Contribution to journalArticle

Francis, JH, Milman, T, Grossniklaus, H, Albert, D, Folberg, R, Levitin, G, Coupland, S, Catalanotti, F, Rabady, D, Kandoth, C, Busam, K & Abramson, D 2019, 'GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas', Ophthalmology. https://doi.org/10.1016/j.ophtha.2018.12.011
Francis, Jasmine H. ; Milman, Tatyana ; Grossniklaus, Hans ; Albert, Daniel ; Folberg, Robert ; Levitin, Gregory ; Coupland, Sarah ; Catalanotti, Federica ; Rabady, David ; Kandoth, Cyriac ; Busam, Klaus ; Abramson, David. / GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas. In: Ophthalmology. 2019.
@article{59f857232aaa46a7ad69089b36340d1c,
title = "GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas",
abstract = "Purpose: GNAQ mutations have been identified in port wine stains (both syndromic and nonsyndromic) and melanocytic ocular neoplasms. This study investigates the presence of GNAQ mutations in diffuse (those associated with Sturge–Weber syndrome [SWS]) and solitary choroidal hemangiomas. Participants: Tissue from 11 patients with the following diagnoses: port wine stain (n = 3), diffuse choroidal hemangioma (n = 1), solitary choroidal hemangioma (n = 6), and choroidal nevus (n = 1). Methods: Ten specimens were interrogated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, a hybridization capture-based next-generation sequencing assay for targeted deep sequencing of all exons and selected introns of 468 key cancer genes in formalin-fixed, paraffin-embedded tumors. Digital polymerase chain reaction was used to detect GNAQ Q209 mutation in 1 specimen. Main Outcome Measures: Detection of GNAQ codon-specific mutation. Results: Activating somatic GNAQ mutations (c.547C > T; p.Arg183Cys) were found in 100{\%} (3 of 3) of the port wine stain and in the diffuse choroidal hemangioma. Somatic GNAQ mutations (c.626A > T; p.Gln209Leu) were found in 100{\%} (6 of 6) of the solitary choroidal hemangiomas and (c.626A > C; p.Gln209Pro) in the choroidal nevus. Conclusions: GNAQ mutations occur in both diffuse and solitary hemangiomas, although at distinct codons. An R183 codon is mutant in diffuse choroidal hemangiomas, consistent with other Sturge–Weber vascular malformations. By contrast, solitary choroidal hemangiomas have mutations in the Q209 codon, similar to other intraocular melanocytic neoplasms.",
author = "Francis, {Jasmine H.} and Tatyana Milman and Hans Grossniklaus and Daniel Albert and Robert Folberg and Gregory Levitin and Sarah Coupland and Federica Catalanotti and David Rabady and Cyriac Kandoth and Klaus Busam and David Abramson",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.ophtha.2018.12.011",
language = "English (US)",
journal = "Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas

AU - Francis, Jasmine H.

AU - Milman, Tatyana

AU - Grossniklaus, Hans

AU - Albert, Daniel

AU - Folberg, Robert

AU - Levitin, Gregory

AU - Coupland, Sarah

AU - Catalanotti, Federica

AU - Rabady, David

AU - Kandoth, Cyriac

AU - Busam, Klaus

AU - Abramson, David

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: GNAQ mutations have been identified in port wine stains (both syndromic and nonsyndromic) and melanocytic ocular neoplasms. This study investigates the presence of GNAQ mutations in diffuse (those associated with Sturge–Weber syndrome [SWS]) and solitary choroidal hemangiomas. Participants: Tissue from 11 patients with the following diagnoses: port wine stain (n = 3), diffuse choroidal hemangioma (n = 1), solitary choroidal hemangioma (n = 6), and choroidal nevus (n = 1). Methods: Ten specimens were interrogated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, a hybridization capture-based next-generation sequencing assay for targeted deep sequencing of all exons and selected introns of 468 key cancer genes in formalin-fixed, paraffin-embedded tumors. Digital polymerase chain reaction was used to detect GNAQ Q209 mutation in 1 specimen. Main Outcome Measures: Detection of GNAQ codon-specific mutation. Results: Activating somatic GNAQ mutations (c.547C > T; p.Arg183Cys) were found in 100% (3 of 3) of the port wine stain and in the diffuse choroidal hemangioma. Somatic GNAQ mutations (c.626A > T; p.Gln209Leu) were found in 100% (6 of 6) of the solitary choroidal hemangiomas and (c.626A > C; p.Gln209Pro) in the choroidal nevus. Conclusions: GNAQ mutations occur in both diffuse and solitary hemangiomas, although at distinct codons. An R183 codon is mutant in diffuse choroidal hemangiomas, consistent with other Sturge–Weber vascular malformations. By contrast, solitary choroidal hemangiomas have mutations in the Q209 codon, similar to other intraocular melanocytic neoplasms.

AB - Purpose: GNAQ mutations have been identified in port wine stains (both syndromic and nonsyndromic) and melanocytic ocular neoplasms. This study investigates the presence of GNAQ mutations in diffuse (those associated with Sturge–Weber syndrome [SWS]) and solitary choroidal hemangiomas. Participants: Tissue from 11 patients with the following diagnoses: port wine stain (n = 3), diffuse choroidal hemangioma (n = 1), solitary choroidal hemangioma (n = 6), and choroidal nevus (n = 1). Methods: Ten specimens were interrogated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, a hybridization capture-based next-generation sequencing assay for targeted deep sequencing of all exons and selected introns of 468 key cancer genes in formalin-fixed, paraffin-embedded tumors. Digital polymerase chain reaction was used to detect GNAQ Q209 mutation in 1 specimen. Main Outcome Measures: Detection of GNAQ codon-specific mutation. Results: Activating somatic GNAQ mutations (c.547C > T; p.Arg183Cys) were found in 100% (3 of 3) of the port wine stain and in the diffuse choroidal hemangioma. Somatic GNAQ mutations (c.626A > T; p.Gln209Leu) were found in 100% (6 of 6) of the solitary choroidal hemangiomas and (c.626A > C; p.Gln209Pro) in the choroidal nevus. Conclusions: GNAQ mutations occur in both diffuse and solitary hemangiomas, although at distinct codons. An R183 codon is mutant in diffuse choroidal hemangiomas, consistent with other Sturge–Weber vascular malformations. By contrast, solitary choroidal hemangiomas have mutations in the Q209 codon, similar to other intraocular melanocytic neoplasms.

UR - http://www.scopus.com/inward/record.url?scp=85059810719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059810719&partnerID=8YFLogxK

U2 - 10.1016/j.ophtha.2018.12.011

DO - 10.1016/j.ophtha.2018.12.011

M3 - Article

C2 - 30537484

AN - SCOPUS:85059810719

JO - Ophthalmology

JF - Ophthalmology

SN - 0161-6420

ER -