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Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma

1
Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
2
Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
3
Department of Clinical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
4
Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1102; https://doi.org/10.3390/cancers11081102
Received: 30 June 2019 / Revised: 16 July 2019 / Accepted: 31 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Uveal Melanoma)
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Abstract

One of the characteristics of prognostically infaust uveal melanoma (UM) is an inflammatory phenotype, which is characterized by high numbers of infiltrating T cells and macrophages, and a high HLA Class I expression. We wondered how this inflammation is regulated, and considered that one of the most important regulators of inflammation, the NFkB pathway, might play a role. We analyzed 64 UM samples for expression of HLA Class I, its regulators, and of members of the NFkB transcription family, using an Illumina HT12V4 array. HLA Class I expression and infiltrating immune cells were also determined by immunohistochemical staining. Information was obtained regarding chromosome status by Affymetrix Nsp array. Our analysis shows that expression of NFkB1, NFkB2 and RELB positively correlates with the level of HLA Class I expression and the number of infiltrating T cells and macrophages, while SPP1 and PPARγ are negatively correlated. Increased levels of NFkB1 and NFkB2 and decreased levels of SPP1 and PPARγ are seen in Monosomy 3/BAP1-negative tumors. This is also the case in non-inflammatory UM, indicating that our observation not only involves infiltrating leukocytes but the tumor cells themselves. We report that the NFkB pathway is associated with inflammation and HLA Class I expression in UM, and is upregulated when BAP1 expression is lost. View Full-Text
Keywords: uveal melanoma; inflammation; HLA Class I; NFkB pathway; BAP1; oncology uveal melanoma; inflammation; HLA Class I; NFkB pathway; BAP1; oncology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Souri, Z.; Wierenga, A.P.A.; van Weeghel, C.; van der Velden, P.A.; Kroes, W.G.M.; Luyten, G.P.M.; van der Burg, S.H.; Jochemsen, A.G.; Jager, M.J. Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma. Cancers 2019, 11, 1102.

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