The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group.

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.

8q Gain Has No Additional Predictive Value in Uveal Melanoma but Is Predictive for a Worse Prognosis in Patients with Uveal Melanoma.

Purpose: Gain of chromosome 8q has been associated with poor prognosis in uveal melanoma (UM), and an increase in the absolute number of 8q-copies correlated with an even shorter survival. Splicing factor 3b subunit 1 ()-mutated () tumors display structural chromosomal anomalies and frequently show a partial gain of chromosome 8qter. A recent subset of UM with early-onset metastases has been identified, prompting the investigation of the relationship between survival, 8q gain, and UM.

Uveal Melanoma Patients Have a Distinct Metabolic Phenotype in Peripheral Blood.

Uveal melanomas (UM) are detected earlier. Consequently, tumors are smaller, allowing for novel eye-preserving treatments. This reduces tumor tissue available for genomic profiling.

Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma.

Approximately 25% of all uveal melanoma (UM) contain driver mutations in the gene encoding the spliceosome factor , and whilst patients with such mutations generally have an intermediate risk on developing metastatic disease, a third of these patients develop early metastasis within 5 years after diagnosis. We therefore investigated whether clinical and/or genetic variables could be indicative of short progression-free survival (PFS < 60 months) or long PFS (PFS ≥ 60 months) for -mutated () UM patients. We collected 146 UM from our Rotterdam Ocular Melanoma Studygroup (ROMS) database and external published datasets.

Genome-wide aberrant methylation in primary metastatic UM and their matched metastases.

Uveal melanoma (UM) is an aggressive intra-ocular cancer with a strong tendency to metastasize. Metastatic UM is associated with mutations in BAP1 and SF3B1, however only little is known about the epigenetic modifications that arise in metastatic UM. In this study we aim to unravel epigenetic changes contributing to UM metastasis using a new genome-wide methylation analysis technique that covers over 50% of all CpG's.

Radiological Patterns of Uveal Melanoma Liver Metastases in Correlation to Genetic Status.

This study reports the role played by the mutation status of Uveal Melanoma (UM) in relation to hepatic metastatic patterns as seen on imaging modalities. Radiological images were obtained from 123 patients treated at the Erasmus Medical Center Rotterdam or the Rotterdam Eye Hospital. Radiological images were derived from either computed tomography or magnetic resonance imaging.

Molecular Genetics of Conjunctival Melanoma and Prognostic Value of Promoter Mutation Analysis.

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering , , , , , , , , , and genes.

Mutations in Uveal Melanoma: A Preference for In-Frame Deletions?

Uveal melanoma (UM) is the most common primary ocular malignancy in adults in the Western world. UM with a mutation in , a spliceosome gene, is characterized by three or more structural changes of chromosome 1, 6, 8, 9, or 11. Also UM without a mutation in harbors similar chromosomal aberrations.

Multi-Modality Analysis Improves Survival Prediction in Enucleated Uveal Melanoma Patients.

Purpose: Uveal melanoma (UM) is characterized by multiple chromosomal rearrangements and recurrent mutated genes. The aim of this study was to investigate if copy number variations (CNV) alone and in combination with other genetic and clinico-histopathological variables can be used to stratify for disease-free survival (DFS) in enucleated patients with UM.

Methods: We analyzed single nucleotide polymorphisms (SNP) array data of primary tumors and other clinical variables of 214 UM patients from the Rotterdam Ocular Melanoma Study (ROMS) cohort.

Aberrant MicroRNA Expression and Its Implications for Uveal Melanoma Metastasis.

Uveal melanoma (UM) is the most frequently found primary intra-ocular tumor in adults. It is a highly aggressive cancer that causes metastasis-related mortality in up to half of the patients. Many independent studies have reported somatic genetic changes associated with high metastatic risk, such as monosomy of chromosome 3 and mutations in .

Chromosomal rearrangements in uveal melanoma: Chromothripsis.

Uveal melanoma (UM) is the most common primary intraocular malignancy in the Western world. Recurrent mutations in GNAQ, GNA11, CYSLTR2, PLCB4, BAP1, EIF1AX, and SF3B1 are described as well as non-random chromosomal aberrations. Chromothripsis is a rare event in which chromosomes are shattered and rearranged and has been reported in a variety of cancers including UM.

Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential.

Purpose: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Iris melanoma comprises 4% to 10% of all UMs and has a lower mortality rate. The genetic changes in iris melanoma are not as well characterized as ciliary body or choroidal melanoma.

Combined mutation and copy-number variation detection by targeted next-generation sequencing in uveal melanoma.

Uveal melanoma is a highly aggressive cancer of the eye, in which nearly 50% of the patients die from metastasis. It is the most common type of primary eye cancer in adults. Chromosome and mutation status have been shown to correlate with the disease-free survival.

Lipomatous Change in Uveal Melanoma: Histopathological, Immunohistochemical and Cytogenetic Analysis.

Purpose: The aim of this study was to describe a case of lipomatous change in uveal melanoma.

Procedures: The patient presented with a 2-year history of blurry vision. A full examination of the right eye revealed a dome-shaped pigmented subretinal mass in the choroid with a thickness of 9 mm and a diameter of 15 mm.

Metastatic Disease in Polyploid Uveal Melanoma Patients Is Associated With BAP1 Mutations.

Purpose: Most of the uvea melanoma (UM) display a near-diploid (normal, -2N) karyotype with only a few chromosomal changes. In contrast to these simple aberrations 18% of the UM samples show a polyploid character (>2N) and this was associated with an unfavorable prognosis. This study attempts to gain insight in the prognostic value of polyploidy in UM.

Uveal Melanomas with SF3B1 Mutations: A Distinct Subclass Associated with Late-Onset Metastases.

Purpose: To investigate the prevalence and prognostic value of SF3B1 and EIF1AX mutations in uveal melanoma (UM) patients.

Design: Case series.

Participants: Cohort of 151 patients diagnosed with and treated for UM.

Risk factors associated with secondary enucleation after fractionated stereotactic radiotherapy in uveal melanoma.

Purpose: To evaluate risk factors for secondary enucleation after fractionated stereotactic radiotherapy (fSRT) in uveal melanoma.

Methods: In this retrospective study, clinical data of 118 consecutive patients who had initially been treated with fSRT between 1999 and 2009 were collected and analysed. The patients who had undergone secondary enucleation were identified and examined for clinical, histopathological and cytogenetical (fluorescence in situ hybridization determined) data.

The prognostic value of extraocular extension in relation to monosomy 3 and gain of chromosome 8q in uveal melanoma.

Purpose: To identify the prognostic value of extraocular extension in enucleated uveal melanoma (UM) patients and to correlate extraocular extension to chromosomal aberrations, metastasis-free survival (MFS), and clinico-histopathological risk factors.

Methods: Retrospective study of patients with UM treated with enucleation between 1987 and 2011. Melanoma-related metastasis and death were recorded.

Chemokine receptor CCR7 expression predicts poor outcome in uveal melanoma and relates to liver metastasis whereas expression of CXCR4 is not of clinical relevance.

Purpose: To examine the prognostic relevance of expression of the chemokine receptors CCR7 and CXCR4 and its ligand CXCL12 in uveal melanoma in nonmetastatic and metastatic patients with correlation to liver metastasis and overall survival.

Methods: Primary uveal melanoma specimens from 19 patients with correlating liver metastasis specimens and 30 primary uveal melanoma specimens of patients without metastasis were collected between the years 1988 and 2008. Expression of CCR7, CXCR4, and CXCL12 were studied using immunohistochemistry.

Patient survival in uveal melanoma is not affected by oncogenic mutations in GNAQ and GNA11.

Background: Mutations in GNAQ and GNA11, encoding the oncogenic G-protein alpha subunit q and 11, respectively, occur frequently in the majority of uveal melanomas.

Methods: Exons 4 and 5 from GNAQ and GNA11 were amplified and sequenced from 92 ciliary body and choroidal melanomas. The mutation status was correlated with disease-free survival (DFS) and other parameters.