Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma

Uveal melanoma is the most common primary ocular malignancy in adults, characterized by gene mutations in G protein subunit alpha q (<i>GNAQ</i>) and G protein subunit alpha 11 (<i>GNA11</i>). Although they are considered to be driver mutations, their role in MUM remains elus...

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Autores principales:	Mizue Terai, Ayako Shimada, Inna Chervoneva, Liam Hulse, Meggie Danielson, Jeff Swensen, Marlana Orloff, Philip B. Wedegaertner, Jeffrey L. Benovic, Andrew E. Aplin, Takami Sato
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	uveal melanoma metastasis metastatic uveal melanoma survival <i>GNA11</i> <i>GNAQ</i> Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/86a4c271f81742bab04b74ded1bf5119
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spelling	oai:doaj.org-article:86a4c271f81742bab04b74ded1bf51192021-11-25T17:03:34ZPrognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma10.3390/cancers132257492072-6694https://doaj.org/article/86a4c271f81742bab04b74ded1bf51192021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5749https://doaj.org/toc/2072-6694Uveal melanoma is the most common primary ocular malignancy in adults, characterized by gene mutations in G protein subunit alpha q (<i>GNAQ</i>) and G protein subunit alpha 11 (<i>GNA11</i>). Although they are considered to be driver mutations, their role in MUM remains elusive. We investigated key somatic mutations of MUM and their impact on patients’ survival after development of systemic metastasis (Met-to-Death). Metastatic lesions from 87 MUM patients were analyzed by next generation sequencing (NGS). <i>GNA11</i> (41/87) and <i>GNAQ</i> (39/87) mutations were most predominantly seen in MUM. Most <i>GNA11</i> mutations were Q209L (36/41), whereas <i>GNAQ</i> mutations comprised Q209L (14/39) and Q209P (21/39). Epigenetic pathway mutations <i>BAP1</i> (42/66), <i>SF3B1</i> (11/66), <i>FBXW7</i> (2/87), <i>PBRM1</i> (1/66), and <i>SETD2</i> (1/66) were found. No specimen had the EIF1AX mutation. Interestingly, Met-to-Death was longer in patients with <i>GNAQ</i> Q209P compared to <i>GNAQ/GNA11</i> Q209L mutations, suggesting the difference in mutation type in <i>GNAQ/GNA11</i> might determine the prognosis of MUM. Structural alterations of the GNAQ/GNA11 protein and their impact on survival of MUM patients should be further investigated.Mizue TeraiAyako ShimadaInna ChervonevaLiam HulseMeggie DanielsonJeff SwensenMarlana OrloffPhilip B. WedegaertnerJeffrey L. BenovicAndrew E. AplinTakami SatoMDPI AGarticleuveal melanomametastasismetastatic uveal melanomasurvival<i>GNA11</i><i>GNAQ</i>Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5749, p 5749 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	uveal melanoma metastasis metastatic uveal melanoma survival <i>GNA11</i> <i>GNAQ</i> Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	uveal melanoma metastasis metastatic uveal melanoma survival <i>GNA11</i> <i>GNAQ</i> Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mizue Terai Ayako Shimada Inna Chervoneva Liam Hulse Meggie Danielson Jeff Swensen Marlana Orloff Philip B. Wedegaertner Jeffrey L. Benovic Andrew E. Aplin Takami Sato Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma
description	Uveal melanoma is the most common primary ocular malignancy in adults, characterized by gene mutations in G protein subunit alpha q (<i>GNAQ</i>) and G protein subunit alpha 11 (<i>GNA11</i>). Although they are considered to be driver mutations, their role in MUM remains elusive. We investigated key somatic mutations of MUM and their impact on patients’ survival after development of systemic metastasis (Met-to-Death). Metastatic lesions from 87 MUM patients were analyzed by next generation sequencing (NGS). <i>GNA11</i> (41/87) and <i>GNAQ</i> (39/87) mutations were most predominantly seen in MUM. Most <i>GNA11</i> mutations were Q209L (36/41), whereas <i>GNAQ</i> mutations comprised Q209L (14/39) and Q209P (21/39). Epigenetic pathway mutations <i>BAP1</i> (42/66), <i>SF3B1</i> (11/66), <i>FBXW7</i> (2/87), <i>PBRM1</i> (1/66), and <i>SETD2</i> (1/66) were found. No specimen had the EIF1AX mutation. Interestingly, Met-to-Death was longer in patients with <i>GNAQ</i> Q209P compared to <i>GNAQ/GNA11</i> Q209L mutations, suggesting the difference in mutation type in <i>GNAQ/GNA11</i> might determine the prognosis of MUM. Structural alterations of the GNAQ/GNA11 protein and their impact on survival of MUM patients should be further investigated.
format	article
author	Mizue Terai Ayako Shimada Inna Chervoneva Liam Hulse Meggie Danielson Jeff Swensen Marlana Orloff Philip B. Wedegaertner Jeffrey L. Benovic Andrew E. Aplin Takami Sato
author_facet	Mizue Terai Ayako Shimada Inna Chervoneva Liam Hulse Meggie Danielson Jeff Swensen Marlana Orloff Philip B. Wedegaertner Jeffrey L. Benovic Andrew E. Aplin Takami Sato
author_sort	Mizue Terai
title	Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma
title_short	Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma
title_full	Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma
title_fullStr	Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma
title_full_unstemmed	Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma
title_sort	prognostic values of g-protein mutations in metastatic uveal melanoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/86a4c271f81742bab04b74ded1bf5119
work_keys_str_mv	AT mizueterai prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT ayakoshimada prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT innachervoneva prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT liamhulse prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT meggiedanielson prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT jeffswensen prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT marlanaorloff prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT philipbwedegaertner prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT jeffreylbenovic prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT andreweaplin prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma AT takamisato prognosticvaluesofgproteinmutationsinmetastaticuvealmelanoma
_version_	1718412787912278016

Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma

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