Next Article in Journal
HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells
Next Article in Special Issue
Families with BAP1-Tumor Predisposition Syndrome in The Netherlands: Path to Identification and a Proposal for Genetic Screening Guidelines
Previous Article in Journal
Coagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation
Previous Article in Special Issue
Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma
Open AccessArticle

Differential Expression of DNA Repair Genes in Prognostically-Favorable versus Unfavorable Uveal Melanoma

1
Department of Ophthalmology, Leiden University Medical Center, 2333 AZ Leiden, The Netherlands
2
Department of Ophthalmology, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
3
Universidade Federal do Rio Grande do Sul, 90040-060 Porto Alegre, Brazil
4
Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130012, China
5
Department of Molecular Cell Biology, Leiden University Medical Center, 2333 AZ Leiden, The Netherlands
6
Center for Reproductive Medicine, Elisabeth-TweeSteden Hospital, 5022 GC Tilburg, The Netherlands
7
Department of Clinical Genetics, Leiden University Medical Center, 2333 AZ Leiden, The Netherlands
8
Department of Translational Research, PSL Research University, Institute Curie, 75248 Paris, France
9
Department of Pathology, Leiden University Medical Center, 2333 AZ Leiden, The Netherlands
10
Laboratory of Tumor Epigenetics, Department of Integrated Oncology Therapies, IRCCS Ospedale Policlinico San Martino, 16133 Genoa, Italy
*
Author to whom correspondence should be addressed.
Mehmet Dogrusöz and Andrea Ruschel Trasel are shared first authors.
Cancers 2019, 11(8), 1104; https://doi.org/10.3390/cancers11081104
Received: 21 June 2019 / Revised: 26 July 2019 / Accepted: 30 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Uveal Melanoma)
Expression of DNA repair genes was studied in uveal melanoma (UM) in order to identify genes that may play a role in metastases formation. We searched for genes that are differentially expressed between tumors with a favorable and unfavorable prognosis. Gene-expression profiling was performed on 64 primary UM from the Leiden University Medical Center (LUMC), Leiden, The Netherlands. The expression of 121 genes encoding proteins involved in DNA repair pathways was analyzed: a total of 44 genes differed between disomy 3 and monosomy 3 tumors. Results were validated in a cohort from Genoa and Paris and the The Cancer Genome Atlas (TCGA) cohort. Expression of the PRKDC, WDR48, XPC, and BAP1 genes was significantly associated with clinical outcome after validation. PRKDC was highly expressed in metastasizing UM (p < 0.001), whereas WDR48, XPC, and BAP1 were lowly expressed (p < 0.001, p = 0.006, p = 0.003, respectively). Low expression of WDR48 and XPC was related to a large tumor diameter (p = 0.01 and p = 0.004, respectively), and a mixed/epithelioid cell type (p = 0.007 and p = 0.03, respectively). We conclude that the expression of WDR48, XPC, and BAP1 is significantly lower in UM with an unfavorable prognosis, while these tumors have a significantly higher expression of PRKDC. Pharmacological inhibition of DNA-PKcs resulted in decreased survival of UM cells. PRKDC may be involved in proliferation, invasion and metastasis of UM cells. Unraveling the role of DNA repair genes may enhance our understanding of UM biology and result in the identification of new therapeutic targets. View Full-Text
Keywords: uveal melanoma; oncology; DNA repair; DNA-PK; PRKDC; BAP1; prognosis uveal melanoma; oncology; DNA repair; DNA-PK; PRKDC; BAP1; prognosis
Show Figures

Graphical abstract

MDPI and ACS Style

Dogrusöz, M.; Ruschel Trasel, A.; Cao, J.; Ҫolak, S.; van Pelt, S.I.; Kroes, W.G.M.; Teunisse, A.F.A.S.; Alsafadi, S.; van Duinen, S.G.; Luyten, G.P.M.; van der Velden, P.A.; Amaro, A.; Pfeffer, U.; Jochemsen, A.G.; Jager, M.J. Differential Expression of DNA Repair Genes in Prognostically-Favorable versus Unfavorable Uveal Melanoma. Cancers 2019, 11, 1104.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Cancers, EISSN 2072-6694, Published by MDPI AG
Back to TopTop