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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.
Afiliação
  • van Weeghel C; Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
  • Wierenga APA; Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
  • Versluis M; Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
  • van Hall T; Department of Clinical Oncology, LUMC, 2333 ZA Leiden, The Netherlands.
  • van der Velden PA; Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
  • Kroes WGM; Department of Clinical Genetics, LUMC, 2333 ZA Leiden, The Netherlands.
  • Pfeffer U; Tumor Epigenetics, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.
  • Luyten GPM; Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
  • Jager MJ; Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. m.j.jager@lumc.nl.
Cancers (Basel) ; 11(8)2019 Aug 07.
Article em En | MEDLINE | ID: mdl-31394807
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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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article