A5069156267- Ocular Oncology and Treatments
- Immunotherapy and Immune Responses
- Esophageal and GI Pathology
- Retinal Development and Disorders
- Microtubule and mitosis dynamics
- Intestinal Malrotation and Obstruction Disorders
- Cutaneous Melanoma Detection and Management
- Cancer Genomics and Diagnostics
- Corneal Surgery and Treatments
- Tracheal and airway disorders
- Cancer-related Molecular Pathways
- Gastroesophageal reflux and treatments
- Pluripotent Stem Cells Research
- HER2/EGFR in Cancer Research
- Muscle Physiology and Disorders
- Veterinary Oncology Research
- Salivary Gland Tumors Diagnosis and Treatment
- MicroRNA in disease regulation
- Glaucoma and retinal disorders
- Renal and related cancers
- Hippo pathway signaling and YAP/TAZ
- Genetic Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- Nanoplatforms for cancer theranostics
- Amyotrophic Lateral Sclerosis Research
Erasmus MC Cancer Institute
2022-2024
Erasmus MC
2016-2024
Erasmus University Rotterdam
2016-2024
Rotterdam University of Applied Sciences
2023
University Medical Center
2023
Erasmus MC - Sophia Children’s Hospital
2022
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 available for molecular characterization due eye-sparing irradiation treatment. This study aimed assess the rise in circulating DNA (ctDNA) levels UM evaluate its efficacy CNV-profiling of patients UM. Methods: In pilot study, we assessed ctDNA blood (n = 18) at various time points, including diagnosis...
Uveal melanoma (UM) is the most frequently found primary intra-ocular tumor in adults. It a highly aggressive cancer that causes metastasis-related mortality up to half of patients. Many independent studies have reported somatic genetic changes associated with high metastatic risk, such as monosomy chromosome 3 and mutations BAP1. Still, mechanisms drive spread are largely unknown. This study aimed elucidate potential role microRNAs metastasis UM. Using next-generation sequencing approach 26...
Uveal melanoma (UM) is an aggressive intra-ocular cancer with a strong tendency to metastasize. Metastatic UM associated mutations in BAP1 and SF3B1, however only little known about the epigenetic modifications that arise metastatic UM. In this study we aim unravel changes contributing metastasis using new genome-wide methylation analysis technique covers over 50% of all CpG's. We identified aberrant SF3B1-mediated metastasis. The data was integrated expression surveyed matched metastases...
The aim of this study was exploration the genetic background conjunctival melanoma (CM) and correlation with recurrent metastatic disease. Twenty-eight CM from Rotterdam Ocular Melanoma Study group were collected DNA isolated formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, TERT genes. Recurrences metastasis present in eight (29%) nine (32%) cases, respectively. promoter...
Approximately 25% of all uveal melanoma (UM) contain driver mutations in the gene encoding spliceosome factor SF3B1, and whilst patients with such SF3B1 generally have an intermediate risk on developing metastatic disease, a third these develop early metastasis within 5 years after diagnosis. We therefore investigated whether clinical and/or genetic variables could be indicative short progression-free survival (PFS < 60 months) or long PFS ≥ for SF3B1-mutated (SF3B1mut) UM patients....
Background: Uveal melanoma (UM) is the most common primary ocular malignancy in adults Western world. UM with a mutation SF3B1, spliceosome gene, characterized by three or more structural changes of chromosome 1, 6, 8, 9, 11. Also without SF3B1 harbors similar chromosomal aberrations. Since, addition to mutations U2AF1 and SRSF2 have also been observed hematological malignancies, mutation-but characteristic pattern-might harbor one these genes. Methods: 42 UMs were selected based on their...
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 in combination with other genetic clinico-histopathological variables can be used stratify for disease-free survival (DFS) enucleated patients UM. Methods: We analyzed single nucleotide polymorphisms (SNP) array data primary tumors clinical 214 UM from the Rotterdam Ocular Melanoma Study (ROMS) cohort....
Uveal melanoma (UM) is a deadly ocular malignancy, originating from uveal melanocytes. Although much known regarding prognostication in UM, the exact mechanism of metastasis mostly unknown. Metastatic tumor cells are to express more stem-like RNA profile which seen often cell-specific embryonic development induce progression. Here, we identified novel transcription regulators by reanalyzing publicly available single cell sequencing experiments. We five interest: ELL2, KDM5B, REXO4, RBFOX2...
Unfortunately, treatment of patients with uveal melanoma (UM) metastatic disease is limited. Twenty percent UM harbor a mutation in the splicing factor gene SF3B1, suggesting that aberrant spliceosome function plays vital role tumorigenesis. Splicing inhibitors exploit preferential sensitivity spliceosome-compromised leukemic cells to these compounds.
Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant hereditary disease caused by a point mutation in exon 17 of the APP gene. We generated human induced pluripotent stem cells (hiPSCs) from symptomatic HCHWA-D patient using non-integrating Sendai virus (SeV). The newly hiPSCs express all pluripotency markers, have normal karyotype, carry Dutch mutation, can differentiate three germ layers vitro and are SeV free.
The prevalence of Barrett's esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than the general population and presents at a younger age (34 vs. 60 years). This (partly) consequence chronic gastroesophageal reflux. Given overlap between genes pathways involved foregut BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes Esophageal biopsies (n = 19, EA/BE); without 44, EA-only) 10, BE-only) were compared...
Facioscapulohumeral dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array on chromosome 4q resulting in sporadic misexpression transcription factor DUX4 skeletal muscle tissue. In ~4% families, de novo contractions occur after fertilization somatic mosaicism with control and FSHD1 cell populations present within same patient. Reprogramming mosaic fibroblasts from two patients into human induced pluripotent stem cells (hiPSCs) generated genetically matched hiPSC lines....
Abstract Uveal melanoma (UM) is the most common primary intraocular malignancy in Western world. Recurrent mutations GNAQ, GNA11, CYSLTR2, PLCB4, BAP1, EIF1AX , and SF3B1 are described as well non‐random chromosomal aberrations. Chromothripsis a rare event which chromosomes shattered rearranged has been reported variety of cancers including UM. SNP arrays 249 UM from patients who underwent enucleation, biopsy or endoresection were reviewed for presence chromothripsis. was defined ten more...
Huntington disease (HD) is an autosomal dominant, neurodegenerative caused by a CAG repeat expansion within the coding sequence of HTT gene, resulting in highly toxic protein with expanded polyglutamine stretch that forms typical aggregates throughout brain. We generated human induced pluripotent stem cells (hiPSCs) from two HD patients using non-integrating Sendai virus (SeV). The hiPSCs display normal karyotype, express all pluripotency markers, have same as original fibroblasts and are...
Abstract Treatment of uveal melanoma (UM) patients with metastatic disease is unfortunately limited. Twenty percent UM harbor a mutation in splicing factor gene SF3B1 , suggesting that aberrant spliceosome functioning plays vital role tumorigenesis. Splicing inhibitors exploit the preferential sensitivity compromised leukemic cells to these compounds. We have studied effect inhibitor E7107 using two cell lines and ex vivo cultured BAP1 mutated primary tumor slices. These slices were exposed...
Abstract Background Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive relationship. A shared etiology makes sense from developmental perspective as both affected structures are foregut derived. genetic component has been described for conditions single entities and EA IHPS variable components in several monogenetic syndromes. We hypothesized that defects disturbing morphogenesis responsible this combination...
Purpose Rationale: In uveal melanoma (UM) non‐random chromosomal aberrations occur and correspond to patients’ prognosis. Mutations in UM specific genes, such as BAP1, SF3B1 EIF1AX are also used predict survival. Aim of this study is identify these mutations corresponding a signature UM. Methods For 277 patients SNP array data ( n = 214) and/or conventional karyotyping 119) the tumor was available. The mutational status known 189 patients. Based on status, analyzed for recurring copy number...
ABSTRACT Patients born with esophageal atresia (EA) have a 30 times higher prevalence of infantile hypertrophic pyloric stenosis (IHPS). This makes sense from developmental perspective as both the esophagus and sphincter are foregut derived structures. EA IHPS variable features in several (monogenetic) syndromes. This, twin familial studies, indicates genetic component for conditions single entities. We hypothesized that defects, disturbing morphogenesis, responsible this combination...
Abstract Aim of the Study Patients born with esophageal atresia (EA) appear to have a 30 times higher prevalence infantile hypertrophic pyloric stenosis (IHPS). This makes sense from developmental perspective as both esophagus and sphincter are foregut derived structures. We hypothesized that genetic defects, disturbing morphogenesis, responsible for specific combination EA IHPS. Methods IHPS between 1970 2017 where possible their parents were included. study was approved by internal review...