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Open AccessArticle

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

1
Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
2
Department of Clinical Oncology, LUMC, 2333 ZA Leiden, The Netherlands
3
Department of Clinical Genetics, LUMC, 2333 ZA Leiden, The Netherlands
4
Tumor Epigenetics, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1127; https://doi.org/10.3390/cancers11081127
Received: 29 June 2019 / Revised: 16 July 2019 / Accepted: 31 July 2019 / Published: 7 August 2019
(This article belongs to the Special Issue Uveal Melanoma)
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Abstract

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. View Full-Text
Keywords: uveal melanoma; mutations; chromosome aberrations; mRNA expression; survival uveal melanoma; mutations; chromosome aberrations; mRNA expression; survival
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van Weeghel, C.; Wierenga, A.P.A.; Versluis, M.; van Hall, T.; van der Velden, P.A.; Kroes, W.G.M.; Pfeffer, U.; Luyten, G.P.M.; Jager, M.J. Do GNAQ and GNA11 Differentially Affect Inflammation and HLA Expression in Uveal Melanoma? Cancers 2019, 11, 1127.

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