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Do GNAQ and GNA11 Differentially Affect Inflammation and HLA Expression in Uveal Melanoma?

Inflammation, characterized by high numbers of infiltrating leukocytes and a high HLA Class I expression, is associated with a bad prognosis in uveal melanoma (UM). We wondered whether mutations in GNA11 or GNAQ differentially affect inflammation and HLA expression, and thereby progression of the di...

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Autores principales: van Weeghel, Christiaan, Wierenga, Annemijn P. A., Versluis, Mieke, van Hall, Thorbald, van der Velden, Pieter A., Kroes, Wilma G. M., Pfeffer, Ulrich, Luyten, Gregorius P. M., Jager, Martine J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721447/
https://www.ncbi.nlm.nih.gov/pubmed/31394807
http://dx.doi.org/10.3390/cancers11081127
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author van Weeghel, Christiaan
Wierenga, Annemijn P. A.
Versluis, Mieke
van Hall, Thorbald
van der Velden, Pieter A.
Kroes, Wilma G. M.
Pfeffer, Ulrich
Luyten, Gregorius P. M.
Jager, Martine J.
author_facet van Weeghel, Christiaan
Wierenga, Annemijn P. A.
Versluis, Mieke
van Hall, Thorbald
van der Velden, Pieter A.
Kroes, Wilma G. M.
Pfeffer, Ulrich
Luyten, Gregorius P. M.
Jager, Martine J.
author_sort van Weeghel, Christiaan
collection PubMed
description Inflammation, characterized by high numbers of infiltrating leukocytes and a high HLA Class I expression, is associated with a bad prognosis in uveal melanoma (UM). We wondered whether mutations in GNA11 or GNAQ differentially affect inflammation and HLA expression, and thereby progression of the disease. We analyzed data of 59 primarily enucleated UM eyes. The type of GNAQ/11 mutation was analyzed using dPCR; chromosome aberrations were determined by Fluorescence in Situ Hybridization (FISH), karyotyping, and single nucleotide polymorphism (SNP) analysis, and mRNA expression by Illumina PCR. Comparing tumors with a GNAQ mutation with those with a GNA11 mutation yielded no significant differences in histopathological characteristics, infiltrate, or HLA expression. When comparing the Q209L mutations with Q209P mutations in tumors with monosomy of chromosome 3, a higher mitotic count was found in the Q209P/M3 tumors (p = 0.007). The Kaplan-Meier (KM) curves between the patients of the different groups were not significantly different. We conclude that the type (Q209P/Q209L) or location of the mutation (GNA11/GNAQ) do not have a significant effect on the immunological characteristics of the tumors, such as infiltrate and HLA Class I expression. Chromosome 3 status was the main determinant in explaining the difference in infiltrate and HLA expression.
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spelling pubmed-67214472019-09-10 Do GNAQ and GNA11 Differentially Affect Inflammation and HLA Expression in Uveal Melanoma? van Weeghel, Christiaan Wierenga, Annemijn P. A. Versluis, Mieke van Hall, Thorbald van der Velden, Pieter A. Kroes, Wilma G. M. Pfeffer, Ulrich Luyten, Gregorius P. M. Jager, Martine J. Cancers (Basel) Article Inflammation, characterized by high numbers of infiltrating leukocytes and a high HLA Class I expression, is associated with a bad prognosis in uveal melanoma (UM). We wondered whether mutations in GNA11 or GNAQ differentially affect inflammation and HLA expression, and thereby progression of the disease. We analyzed data of 59 primarily enucleated UM eyes. The type of GNAQ/11 mutation was analyzed using dPCR; chromosome aberrations were determined by Fluorescence in Situ Hybridization (FISH), karyotyping, and single nucleotide polymorphism (SNP) analysis, and mRNA expression by Illumina PCR. Comparing tumors with a GNAQ mutation with those with a GNA11 mutation yielded no significant differences in histopathological characteristics, infiltrate, or HLA expression. When comparing the Q209L mutations with Q209P mutations in tumors with monosomy of chromosome 3, a higher mitotic count was found in the Q209P/M3 tumors (p = 0.007). The Kaplan-Meier (KM) curves between the patients of the different groups were not significantly different. We conclude that the type (Q209P/Q209L) or location of the mutation (GNA11/GNAQ) do not have a significant effect on the immunological characteristics of the tumors, such as infiltrate and HLA Class I expression. Chromosome 3 status was the main determinant in explaining the difference in infiltrate and HLA expression. MDPI 2019-08-07 /pmc/articles/PMC6721447/ /pubmed/31394807 http://dx.doi.org/10.3390/cancers11081127 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
van Weeghel, Christiaan
Wierenga, Annemijn P. A.
Versluis, Mieke
van Hall, Thorbald
van der Velden, Pieter A.
Kroes, Wilma G. M.
Pfeffer, Ulrich
Luyten, Gregorius P. M.
Jager, Martine J.
Do GNAQ and GNA11 Differentially Affect Inflammation and HLA Expression in Uveal Melanoma?
title Do GNAQ and GNA11 Differentially Affect Inflammation and HLA Expression in Uveal Melanoma?
title_full Do GNAQ and GNA11 Differentially Affect Inflammation and HLA Expression in Uveal Melanoma?
title_fullStr Do GNAQ and GNA11 Differentially Affect Inflammation and HLA Expression in Uveal Melanoma?
title_full_unstemmed Do GNAQ and GNA11 Differentially Affect Inflammation and HLA Expression in Uveal Melanoma?
title_short Do GNAQ and GNA11 Differentially Affect Inflammation and HLA Expression in Uveal Melanoma?
title_sort do gnaq and gna11 differentially affect inflammation and hla expression in uveal melanoma?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721447/
https://www.ncbi.nlm.nih.gov/pubmed/31394807
http://dx.doi.org/10.3390/cancers11081127
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