Methylated CfDNA may distinguish between high- and intermediate-risk uveal melanoma: a pilot study Mike Wu, Daniël P. de Bruyn, Ruben G. Boers, Aaron B. Beasley, Daan M. Hazelaar, Stavros Makrodimitris, Joachim B. Boers, Jolanda Vaarwater, Ronald O.B. de Keizer, Robert M. Verdijk, Nicole C. Naus, Dion Paridaens, Saskia M. Wilting, Elin S. Gray, Wilfred F.J. van IJcken, Joost Gribnau, Annelies de Klein, Erwin Brosens, Emine Kiliç, and Cancer Cell International, 2026 BACKGROUND: Uveal melanoma (UM) is a highly aggressive malignancy with a metastatic risk that depends on the molecular subclass. This subclass can be determined through molecular characterization of tumor-derived tissue. With eye-sparing treatments, tumor tissue is rarely available for molecular testing. We hypothesized that minimal invasive biomarkers such as methylated cell-free DNA (cfDNA) or circulating tumor DNA (ctDNA) can be used for prognosis and monitoring of patients. METHODS: Plasma cfDNA was isolated from healthy blood donors (HBDs, N = 19) and UM patients (N = 22). Plasma was collected at baseline (localized disease, N = 13) and during follow-up (metastatic disease, N = 9) from independent patients with high metastatic risk (HR, N = 11) (monosomy 3 and/or BAP1-mutated tumor) or intermediate metastatic risk (IR, N = 11) (disomy 3 and/or SF3B1-mutated tumor). Methylation signatures were determined using genome-wide LpnPI-based methylated DNA sequencing (MeD-seq). Samples with a CpG/reads ratio < 20% (N = 3) were excluded. IchorCNA was used to estimate the tumor fraction. cfDNA samples with detectable tumor fraction (N = 2) were analyzed separately from the other cfDNA samples without detectable tumor fraction (N = 18) to reduce noise in downstream analyses. Differentially methylated regions (DMRs) were identified between the following predefined subgroups: UM (N = 11) vs. HBDs (N = 19), and HR (N = 10) vs. IR (N = 7). To visualize clustering, principal component analysis (PCA) and hierarchical clustering was performed on the DMRs with fold change > 2.0. Gene set enrichment analysis (GSEA, Z-score > 2.0 and p < 0.05) was performed to evaluate biological relevance. RESULTS: Distinct clustering was observed between UM and HBDs samples, and between HR and IR samples, although outliers were present in the latter comparison. GSEA implicated eight canonical pathways including the S100 Family Signaling Pathway and RAF/MAP kinase cascade, which are linked to tumorigenesis and immune processes. CONCLUSION: This pilot study reports on cfDNA methylation signatures that differentiates UM patients from HBDs, and may distinguish between intermediate and high risk UM subgroups, supporting its prognostic potential. However, its role in monitoring disease progression requires further validation. Independent replication studies are warranted to confirm our findings and evaluate the clinical applicability in UM.
Circulating Tumor Cells in Uveal Melanoma: Multi-Marker Detection and Association With Disease State Daniel P. de Bruyn, Fabiana Lucia Bassil, Mike Wu, Aaron B. Beasley, Jolanda Vaarwater, Mai N. Van, Jaco Kraan, Robert M. Verdijk, Dion Paridaens, Caroline M. van Rij, Nicole C. Naus, Annelies de Klein, Elin S. Gray, Erwin Brosens, Emine Kiliç Investigative Ophthalmology and Visual Science, 2026 Purpose: Uveal melanoma (UM) is primarily treated with eye-sparing radiotherapy, leaving limited tumor tissue for molecular analysis. Circulating tumor cells (CTCs) may offer a minimally invasive alternative for genomic tumor profiling. This pilot study evaluated the feasibility of a multi-marker CTC capture approach in UM patients at diagnosis, during fractionated stereotactic radiotherapy (fSRT), and at metastatic progression. Methods: Patients with localized or metastatic UM were prospectively enrolled. Peripheral blood samples were collected at baseline, during fSRT, and on detection of metastases. CTCs were captured and enumerated using a multi-marker approach and fluorescence microscopy. Results: A total of 76 patients were included: 68 with localized disease and eight with metastatic disease. Four patients presented initially with localized disease but developed metastasis during follow-up: for comparisons, only metastatic-stage samples were used, yielding 64 localized and 12 metastatic samples. CTCs were detected in 69.1% of patients with localized disease at baseline and in 83.3% of those with metastases. CTC counts were significantly higher in metastatic disease than in localized disease (median = 8 vs. 3; P = 0.010). Among patients undergoing fSRT, paired analysis showed a significant increase in CTC counts between day 3 and day 5 (median = 1 vs. 4; P = 0.007). No significant associations were observed between baseline CTC counts and tumor thickness, largest basal diameter, tumor volume, American Joint Committee on Cancer tumor stage, tumor location, or molecular risk class. Conclusions: Multi-marker CTC detection in UM patients is feasible across disease stages. Increased CTC counts during fSRT may offer a window for molecular characterization. Larger studies with longitudinal blood sampling are needed to validate clinical and prognostic utility.
Stereotactic Radiation Therapy or Protons for Uveal Melanoma Patients? An Artificial Intelligence (AI)-Based Clinical Treatment Decision-Making Tool Predicting Doses To Radiation Therapy Constraints Emmanuelle Fleury, Jean-Philippe Pignol, Emine Kiliç, Caroline van Rij, Nicole Naus, Serdar Yavuzyigitoglu, Wilhelm den Toom, Andras Zolnay, Kees Spruijt, Marco van Vulpen, Petra Trnková, Mischa Hoogeman International Journal of Radiation Oncology Biology Physics, 2025 PURPOSE: For ocular melanoma, selecting between stereotactic radiation therapy (SRT) and protons requires a lengthy plan comparison process. The purpose of this brief report is to describe an artificial intelligence (AI) decision-making tool to predict dosimetric and clinical outcomes based on easy-to-access tumor characteristics. METHODS AND MATERIALS: The AI tool was based on a retrospective database of 66 patients with uveal melanoma treated in a single center with robotic SRT. A supervised machine learning model was developed to correlate the risk of toxicity for each radiation modality and clinical features. Clinical toxicity risks were built in various profiles: Profile I for maculopathy, optic-neuropathy, and visual acuity deterioration; Profile II for neovascular glaucoma; Profile III for radiation-induced retinopathy; and Profile IV for dry-eye syndrome. RESULTS: Machine learning-based toxicity prediction accuracy for selecting the correct treatment modality was 81%, 77%, 91%, and 93% for Profiles I, II, III, and IV, respectively. CONCLUSION: The study shows that a machine learning method based on easy-to-access clinical characteristics can predict which toxicity would be greater with SRT or protons. This AI tool could support patients in making informed treatment decisions in an ophthalmology clinic, without the lengthy wait for computed tomographic simulation results and extensive plan comparisons.
Two Cases of Intraocular Undifferentiated Pleomorphic Sarcoma Sodaba Khatab, Johanna Maria Colijn, Nicole Naus, Robert M. Verdijk, Gijsbert Hötte Ocular Oncology and Pathology, 2024 Introduction: Undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma, is a high-grade soft tissue sarcoma arising from mesenchymal stem cells. UPSs are rare and account for about 5% of all soft tissue sarcoma. UPSs arising in the head and neck are especially rare, comprising 1–3% of all UPSs. Case Presentation: In this report, we describe 2 cases of intraocular UPS. Both cases concern 68-year-old males: one developing a UPS in an eviscerated socket after a chronic fibrinous inflammation and the other years after ocular trauma. Conclusion: Our cases may support the hypothesis of chronic inflammation playing a role in sarcoma formation as they are characterized by a longstanding history of (surgical) trauma with signs of chronic inflammation and phthisis bulbi.
Comparison of stereotactic radiotherapy and protons for uveal melanoma patients Emmanuelle Fleury, Jean-Philippe Pignol, Emine Kiliç, Maaike Milder, Caroline van Rij, Nicole Naus, Serdar Yavuzyigitoglu, Wilhelm den Toom, Andras Zolnay, Kees Spruijt, Marco van Vulpen, Petra Trnková, Mischa Hoogeman Physics and Imaging in Radiation Oncology, 2024 Background and purpose: Uveal melanoma (UM) is the most common primary ocular malignancy. We compared fractionated stereotactic radiotherapy (SRT) with proton therapy, including toxicity risks for UM patients. Materials and methods: For a total of 66 UM patients from a single center, SRT dose distributions were compared to protons using the same planning CT. Fourteen dose-volume parameters were compared in 2-Gy equivalent dose per fraction (EQD2). Four toxicity profiles were evaluated: maculopathy, optic-neuropathy, visual acuity impairment (Profile I); neovascular glaucoma (Profile II); radiation-induced retinopathy (Profile III); and dry-eye syndrome (Profile IV). For Profile III, retina Mercator maps were generated to visualize the geographical location of dose differences. Results: In 9/66 cases, (14 %) proton plans were superior for all dose-volume parameters. Higher T stages benefited more from protons in Profile I, especially tumors located within 3 mm or less from the optic nerve. In Profile II, only 9/66 cases resulted in a better proton plan. In Profile III, better retina volume sparing was always achievable with protons, with a larger gain for T3 tumors. In Profile IV, protons always reduced the risk of toxicity with a median RBE-weighted EQD2 reduction of 15.3 Gy. Conclusions: This study reports the first side-by-side imaging-based planning comparison between protons and SRT for UM patients. Globally, while protons appear almost always better regarding the risk of optic-neuropathy, retinopathy and dry-eye syndrome, for other toxicity like neovascular glaucoma, a plan comparison is warranted. Choice would depend on the prioritization of risks.
The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group Natasha M. van Poppelen, Nathalie Cassoux, Joni A. Turunen, Nicole C. Naus, Robert M. Verdijk, Jolanda Vaarwater, Victoria Cohen, Vasilios P. Papastefanou, Hayyam Kiratli, Svetlana V. Saakyan, Alexander Y. Tsygankov, Iwona Rospond-Kubiak, Hardeep S. Mudhar, Sachin M. Salvi, Jens F. Kiilgaard, Steffen Heegaard, Alexandre P. Moulin, Maria A. Saornil, Ciro Garciá-Alvarez, Maria Fili, Nils A. Eide, Peter Meyer, Tero T. Kivelä, Annelies de Klein, Emine Kilic, Rana'a T. Al-Jamal Investigative Ophthalmology and Visual Science, 2024 Purpose To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. Methods Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. Results The mean age at diagnosis was 17 years (range 5.0–24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). Conclusions We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).
8q Gain Has No Additional Predictive Value in SF3B1MUT Uveal Melanoma but Is Predictive for a Worse Prognosis in Patients with BAP1MUT Uveal Melanoma Josephine Q.N. Nguyen, Wojtek Drabarek, Jolanda Vaarwater, Serdar Yavuzyigitoglu, Robert M. Verdijk, Dion Paridaens, Nicole C. Naus, Annelies de Klein, Erwin Brosens, Emine Kiliç, Emine Kilic, Annelies de Klein, Erwin Brosens, Nicole C. Naus, Dion Paridaens, Serdar Yavuzyigitoglu, Wojtek Drabarek, Josephine Q.N. Nguyen, Jolanda Vaarwater, Robert M. Verdijk Ophthalmology Science, 2024 PurposeGain of chromosome 8q has been associated with poor prognosis in uveal melanoma (UM), and an increase in absolute number of 8q-copies correlated with an even shorter survival. SF3B1-mutated (SF3B1MUT) tumors display structural chromosomal anomalies and frequently show partial gain of chromosome 8qter. A recent subset of SF3B1MUT UM with early-onset metastases has been identified, prompting the investigation of the relationship between survival, 8q gain and SF3B1MUT UM.DesignRetrospective cohort study.SubjectsPatients diagnosed with UM and who underwent enucleation or received a biopsy at the Erasmus MC Cancer Institute or the Rotterdam Eye Hospital, The Netherlands were included.MethodsFifty-nine patients with SF3B1MUT tumors and 211 patients with BAP1MUT tumors were included in this study. Copy number status and gene expression were assessed using single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH) and/or karyotyping. Disease-free survival (DFS) was determined and a cut-off of 60 months was used to define early-onset metastatic disease.Main outcome measuresDisease-free survival.ResultsForty-eight patients with SF3B1MUT UM (81%) had chromosome 8q gain (3 copies, 78%; 4 copies, 22%). Kaplan-Meier analysis of SF3B1MUT UM did not indicate a difference in survival in patients with or without gain of 8q (p=0.99). Furthermore, the number of 8q copies was not associated with survival when comparing early (p=0.97) vs late (p=0.23) metastases group. In contrast, presence of 8q gain (86%) was correlated with a decreased survival in BAP1MUT UM (p=0.013).ConclusionsWe did not find a correlation between 8q gain and early-onset metastasis in SF3B1MUT tumors. Gain of 8q has no additional predictive value in SF3B1MUT tumors. In contrast, 8q gain is predictive for a worse prognosis in patients with BAP1MUT tumors. Thus, gain of chromosome 8q has additional predictive value for BAP1MUT tumors, but not for SF3B1MUT tumors.
Evaluation of Circulating Tumor DNA as a Liquid Biomarker in Uveal Melanoma Daniel P. de Bruyn, Natasha M. van Poppelen, Tom Brands, Susanne C. van den Boom, Ellis Eikenboom, Anja Wagner, Monique M. van Veghel-Plandsoen, Geert Geeven, Berna Beverloo, Caroline M. van Rij, Robert M. Verdijk, Nicole C. Naus, Mette M. Bagger, Jens F. Kiilgaard, Annelies de Klein, Erwin Brosens, Emine Kiliç Investigative Ophthalmology and Visual Science, 2024 Purpose Uveal melanoma (UM) has a high propensity to metastasize. Prognosis is associated with specific driver mutations and copy number variations (CNVs), but limited primary tumor tissue is available for molecular characterization due to eye-sparing irradiation treatment. This study aimed to assess the rise in circulating tumor DNA (ctDNA) levels in UM and evaluate its efficacy for CNV-profiling of patients with UM. Methods In a pilot study, we assessed ctDNA levels in the blood of patients with UM (n = 18) at various time points, including the time of diagnosis (n = 13), during fractionated stereotactic radiotherapy (fSRT) treatment (n = 6), and upon detection of metastatic disease (n = 13). Shallow whole-genome sequencing (sWGS) combined with in silico size-selection was used to identify prognostically relevant CNVs in patients with UM (n = 26) from peripheral blood retrieved at the time of diagnosis (n = 9), during fSRT (n = 5), during post-treatment follow-up (n = 4), metastasis detection (n = 6), and metastasis follow-up (n = 4). Results A total of 34 patients had blood analyzed for ctDNA detection (n = 18) and/or CNV analysis (n = 26) at various time points. At the time of diagnosis, 5 of 13 patients (38%) had detectable ctDNA (median = 0 copies/mL). Upon detection of metastatic disease, ctDNA was detected in 10 of 13 patients (77%) and showed increased ctDNA levels (median = 24 copies/mL, P < 0.01). Among the six patients analyzed during fSRT, three (50%) patients had detectable ctDNA at baseline and three of six (50%) patients had undetectable levels of ctDNA. During the fSRT regimen, ctDNA levels remained unchanged (P > 0.05). The ctDNA fractions were undetectable to low in localized disease, and sWGS did not elucidate chromosome 3 status from blood samples. However, in 7 of 10 (70%) patients with metastases, the detection of chromosome 3 loss corresponded to the high metastatic-risk class. Conclusions The rise in ctDNA levels observed in patients with UM harboring metastases suggests its potential utility for CNV profiling. These findings highlight the potential of using ctDNA for metastasis detection and patient inclusion in therapeutic studies targeting metastatic UM.
Time Trends in the Treatment and Survival of 5036 Uveal Melanoma Patients in The Netherlands over a 30-Year Period Thaïs M. L. Tong, Esther Bastiaannet, Frank M. Speetjens, Christian U. Blank, Gregorius P. M. Luyten, Martine J. Jager, Marina Marinkovic, T. H. Khanh Vu, Coen R. N. Rasch, Carien L. Creutzberg, Jan-Willem M. Beenakker, Henk H. Hartgrink, Jacobus J. J. Bosch, Emine Kiliç, Nicole C. Naus, Serdar Yavuzyigitoglu, Caroline M. van Rij, Mark C. Burgmans, Ellen H. W. Kapiteijn Cancers, 2023 Background: Uveal melanoma (UM) is a rare intraocular tumor with a dismal prognosis once metastasized. This study provides a nationwide overview and time trends of patients diagnosed with primary UM in the Netherlands between 1989 and 2019. Methods: A retrospective population-based cohort study based on patients with primary UM from the database of the Netherlands Cancer Registry (NCR), linked with the national population registry Statistics Netherlands on inhabitants’ cause of death. Two time periods (1989–2004, 2005–2019) were compared with descriptive statistics. Kaplan–Meier and (multivariate) Cox proportional hazard models were used to assess changes over time for overall survival (OS) and cancer-specific survival (CSS). Results: In total, 5036 patients were analyzed with a median age of 64.0 years at the time of diagnosis. The number of patients increased over time. In the first (1989–2004) and second (2005–2019) period, 32% versus 54% of the patients received radiotherapy (p < 0.001). The median FU time was 13.4 years. The median OS of the first and second periods was 9.5 (95% CI 8.7–10.3) versus 11.3 years (95% CI 10.3–12.3; p < 0.001). The median CSS was 30.0 years (95% CI NA) in the first period and not reached in the second period (p = 0.008). In multivariate analysis (MVA), female gender (HR 0.85; 95% CI 0.79–0.92, p < 0.001) and radiotherapy treatment (HR 0.73; 95% CI 0.64–0.83, p < 0.001) were associated with better OS. Radiotherapy treatment (HR 0.74; 95% CI 0.61–0.90, p = 0.002) was also associated with better CSS. The period of diagnosis was not associated with OS or CSS. Conclusions: In this study of patients with primary UM, there was a shift to the diagnosis of smaller tumors, possibly due to stage migration. There was also an increase in eye-preserving treatments over time. OS and CSS were modestly improved in the second time period; however, the time period was not associated with OS or CSS in multivariate analyses.
ATRX Loss in the Development and Prognosis of Conjunctival Melanoma Jolique A. van Ipenburg, Quincy C. C. van den Bosch, Dion Paridaens, Hendrikus J. Dubbink, Emine Kiliç, Nicole Naus, Robert M. Verdijk International Journal of Molecular Sciences, 2023 Metastatic disease is linked to TERT promoter mutations in conjunctival melanomas (CM). Both TERT promoter and ATRX mutations are associated with faulty telomere maintenance. This study aimed to determine the prognostic value of ATRX loss in conjunctival melanocytic lesions. Eighty-six conjunctival melanocytic lesions from the Rotterdam Ocular Melanoma Study group were collected. ATRX status and TERT promoter status were determined using immunohistochemical staining and molecular diagnostics, respectively. None of the nevi (n = 16) and primary acquired melanosis (PAM) without atypia (n = 6) showed ATRX loss. ATRX loss was found in 2/5 PAM with atypia without CM and in 8/59 CM. No cases with a TERT promoter mutation (n = 26) showed ATRX loss. Eight/eleven metastatic CM harbored a TERT promoter mutation, two other metastatic CM showed ATRX loss and one metastatic case showed no TERT promoter/ATRX alterations. In conclusion ATRX loss and TERT promoter mutations are only found in (pre)malignant conjunctival melanocytic lesions, with most metastatic cases harboring one of these alterations, suggesting that both alterations are associated with adverse behavior. Similar to TERT promoter mutations, ATRX loss may be used as a diagnostic tool in determining whether a conjunctival melanocytic lesion is prone to having an adverse course.
Uveal Melanoma Patients Have a Distinct Metabolic Phenotype in Peripheral Blood Daniël P. de Bruyn, Michiel Bongaerts, Ramon Bonte, Jolanda Vaarwater, Magda A. Meester-Smoor, Robert M. Verdijk, Dion Paridaens, Nicole C. Naus, Annelies de Klein, George J. G. Ruijter, Emine Kiliç, Erwin Brosens International Journal of Molecular Sciences, 2023
Ophthalmological Findings in Youths with a Newly Diagnosed Brain Tumor Myrthe A. Nuijts, Inge Stegeman, Tom van Seeters, Marloes D. Borst, Carlien A. M. Bennebroek, Dennis R. Buis, Nicole C. Naus, Giorgio L. Porro, Michelle B. van Egmond-Ebbeling, Elisabeth S. M. Voskuil-Kerkhof, JanWillem R. Pott, Niels E. Franke, Evelien de Vos-Kerkhof, Eelco W. Hoving, Antoinette Y. N. Schouten-van Meeteren, Saskia M. Imhof JAMA Ophthalmology, 2022
Outcome after treatment for sebaceous carcinoma: A multicenter study Eva Huis In 't Veld, Ronald Keizer, Nicoline Post, Jeroen Versteeg, Robert Verdijk, Nicole Naus, Germaine Relyveld, Marianne Crijns, Myles Smith, Dirk Grünhagen, Marlies Wakkee, Dion Paridaens, Ioannis Zavrakidis, Antien Mooyaart, Alexander van Akkooi, Dirk Strauss, Cornelis Verhoef, Michel Wouters, Andrew Hayes, Winan van Houdt Journal of Surgical Oncology, 2022
Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma Wojtek Drabarek, Job van Riet, Josephine Q. N. Nguyen, Kyra N. Smit, Natasha M. van Poppelen, Rick Jansen, Eva Medico-Salsench, Jolanda Vaarwater, Frank J. Magielsen, Tom Brands, Bert Eussen, Thierry. P. P. van den Bosch, Robert M. Verdijk, Nicole C. Naus, Dion Paridaens, Annelies de Klein, Erwin Brosens, Harmen J. G. van de Werken, Emine Kilic, and Cancers, 2022
The sebaceous gland carcinoma Nederlands Tijdschrift Voor Dermatologie En Venereologie, 2022
Molecular genetics of conjunctival melanoma and prognostic value of tert promoter mutation analysis Natasha M. van Poppelen, Jolique A. van Ipenburg, Quincy van den Bosch, Jolanda Vaarwater, Tom Brands, Bert Eussen, Frank Magielsen, Hendrikus J. Dubbink, Dion Paridaens, Erwin Brosens, Nicole Naus, Annelies de Klein, Emine Kiliç, Robert M. Verdijk International Journal of Molecular Sciences, 2021
Spliceosome mutations in uveal melanoma Josephine Q.N. Nguyen, Wojtek Drabarek, Serdar Yavuzyigitoglu, Eva Medico Salsench, Robert M. Verdijk, Nicole C. Naus, Annelies de Klein, Emine Kiliç, Erwin Brosens International Journal of Molecular Sciences, 2020
MicroRNA Profiling in Benign and Malignant Conjunctival Melanocytic Lesions Jolique A. van Ipenburg, Ad J.M. Gillis, Ing, Lambert C.J. Dorssers, Quincy C.C. van den Bosch, Rita van Ginderdeuren, Guy S. Missotten, Nicole Naus, Dion Paridaens, Leendert H.J. Looijenga, Robert M. Verdijk Ophthalmology, 2020
Families with BAP1-tumor predisposition syndrome in The Netherlands: Path to identification and a proposal for genetic screening guidelines Cindy Chau, Remco van Doorn, Natasha M. van Poppelen, Nienke van der Stoep, Arjen R. Mensenkamp, Rolf H. Sijmons, Barbara W. van Paassen, Ans M. W. van den Ouweland, Nicole C. Naus, Annemieke H. van der Hout, Thomas P. Potjer, Fonnet E. Bleeker, Marijke R. Wevers, Liselotte P. van Hest, Marjolijn C. J. Jongmans, Marina Marinkovic, Jaco C. Bleeker, Martine J. Jager, Gregorius P. M. Luyten, Maartje Nielsen Cancers, 2019
Multi-modality analysis improves survival prediction in enucleated uveal melanoma patients Wojtek Drabarek, Serdar Yavuzyigitoglu, Askar Obulkasim, Job van Riet, Kyra N. Smit, Natasha M. van Poppelen, Jolanda Vaarwater, Tom Brands, Bert Eussen, Robert M. Verdijk, Nicole C. Naus, Hanneke W. Mensink, Dion Paridaens, Eric Boersma, Harmen J. G. van de Werken, Emine Kilic, Annelies de Klein, and Investigative Ophthalmology and Visual Science, 2019
Correlation of Gene Mutation Status with Copy Number Profile in Uveal Melanoma Serdar Yavuzyigitoglu, Wojtek Drabarek, Kyra N. Smit, Natasha van Poppelen, Anna E. Koopmans, Jolanda Vaarwater, Tom Brands, Bert Eussen, Hendrikus J. Dubbink, Job van Riet, Harmen J.G. van de Werken, Berna Beverloo, Robert M. Verdijk, Nicole Naus, Dion Paridaens, Emine Kilic, Annelies de Klein Ophthalmology, 2017
Adjuvant Dendritic Cell Vaccination in High-Risk Uveal Melanoma Kalijn F. Bol, Thomas van den Bosch, Gerty Schreibelt, Hanneke W. Mensink, Jan E.E. Keunen, Emine Kiliç, Wouter J. Japing, Kaspar W. Geul, Harm Westdorp, Steve Boudewijns, Sandra A.J. Croockewit, Michelle M. van Rossum, Anna L. de Goede, Nicole C. Naus, Winette T.A. van der Graaf, Winald R. Gerritsen, Annelies de Klein, Cornelis J.A. Punt, Carl G. Figdor, Victoria M. Cohen, Dion Paridaens, I. Jolanda M. de Vries Ophthalmology, 2016
Metastatic disease in polyploid uveal melanoma patients is associated with BAP1 mutations Serdar Yavuzyigitoglu, Hanneke W. Mensink, Kyra N. Smit, Jolanda Vaarwater, Robert M. Verdijk, Berna Beverloo, Hennie T. Brüggenwirth, Ronald van Marion, Hendrikus J. Dubbink, Dion Paridaens, Nicole C. Naus, Annelies de Klein, Emine Kiliç Investigative Ophthalmology and Visual Science, 2016
Lacrimal Gland Radiosensitivity in Uveal Melanoma Patients Karin Muller, Peter J.C.M. Nowak, Nicole Naus, Connie de Pan, Cornelis A. van Santen, Peter Levendag, Gré P.M. Luyten International Journal of Radiation Oncology Biology Physics, 2009
Chromosome 3 intratumor heterogeneity in uveal melanoma Hanneke W. Mensink, Jolanda Vaarwater, Emine Kilic¸, Nicole C. Naus, Neeltje Mooy, Gre Luyten, Hennie T. Bru¨ggenwirth, Dion Paridaens, Annelies de Klein Investigative Ophthalmology and Visual Science, 2009
