Do GNAQ and GNA11 differentially affect inflammation and HLA expression in uveal melanoma?

Christiaan van Weeghel, Annemijn P.A. Wierenga, Mieke Versluis, Thorbald van Hall, Pieter A. van der Velden, Wilma G.M. Kroes, Ulrich Pfeffer, Gregorius P.M. Luyten, Martine J. Jager

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number1127
JournalCancers
Volume11
Issue number8
DOIs
Publication statusPublished - Aug 1 2019

Fingerprint

Inflammation
Mutation
Chromosomes, Human, Pair 3
Neoplasms
Monosomy
Karyotyping
Uveal melanoma
Fluorescence In Situ Hybridization
Leukocyte Count
Chromosome Aberrations
Single Nucleotide Polymorphism
Disease Progression
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Chromosome aberrations
  • MRNA expression
  • Mutations
  • Survival
  • Uveal melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

van Weeghel, C., Wierenga, A. P. A., Versluis, M., van Hall, T., van der Velden, P. A., Kroes, W. G. M., ... Jager, M. J. (2019). Do GNAQ and GNA11 differentially affect inflammation and HLA expression in uveal melanoma? Cancers, 11(8), [1127]. https://doi.org/10.3390/cancers11081127

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.

In: Cancers, Vol. 11, No. 8, 1127, 01.08.2019.

Research output: Contribution to journalArticle

van Weeghel, C, Wierenga, APA, Versluis, M, van Hall, T, van der Velden, PA, Kroes, WGM, Pfeffer, U, Luyten, GPM & Jager, MJ 2019, 'Do GNAQ and GNA11 differentially affect inflammation and HLA expression in uveal melanoma?', Cancers, vol. 11, no. 8, 1127. https://doi.org/10.3390/cancers11081127
van Weeghel C, Wierenga APA, Versluis M, van Hall T, van der Velden PA, Kroes WGM et al. Do GNAQ and GNA11 differentially affect inflammation and HLA expression in uveal melanoma? Cancers. 2019 Aug 1;11(8). 1127. https://doi.org/10.3390/cancers11081127
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?. In: Cancers. 2019 ; Vol. 11, No. 8.
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