- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- BRCA gene mutations in cancer
- Bioinformatics and Genomic Networks
- Genetic factors in colorectal cancer
- Cancer-related molecular mechanisms research
- Breast Cancer Treatment Studies
- Estrogen and related hormone effects
- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Gene expression and cancer classification
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Cytokine Signaling Pathways and Interactions
- MicroRNA in disease regulation
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Molecular Biology Techniques and Applications
- Circular RNAs in diseases
- Ferroptosis and cancer prognosis
- Genomics and Chromatin Dynamics
Erasmus MC
2015-2025
Erasmus MC Cancer Institute
2015-2024
Cancer Genomics Centre
2008-2023
Philips (United States)
2023
Erasmus University Rotterdam
2004-2019
Amsterdam UMC Location Vrije Universiteit Amsterdam
2019
Maastricht University
2019
Oncode Institute
2019
The Netherlands Cancer Institute
2019
Elisabeth-TweeSteden Ziekenhuis
2019
Abstract We explored whether the five previously reported molecular subtypes in breast cancer show a preference for organ-specific relapse and searched pathways involved. The “intrinsic” gene list describing was used to classify 344 primary tumors of lymph node–negative patients. Fisher exact tests were determine association between tumor subtype particular site distant these patients who only received local treatment. Modulated genes identified various groups using Significance Analysis...
In this study, we quantified 249 mature micro-RNA (miRNA) transcripts in estrogen receptor-positive (ER + ) primary breast tumors of patients with lymph node-negative (LNN) disease to identify miRNAs associated metastatic capability. addition, the prognostic value candidate was determined ER − /LNN cancer. Unsupervised analysis a prescreening set 38 identified three subgroups predominantly driven by miRNA signatures: an ER-driven luminal B-associated signature, stromal and overexpressed...
Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in Western world. Therapeutic approaches need to account for inter-patient intra-tumoural heterogeneity detailed characterization of vitro models representing different histological molecular subtypes critical enable reliable preclinical testing. There are approximately 100 publicly available cell lines but their cellular characteristics largely undescribed. We have characterized...
The biology of tumors relapsing to bone is poorly understood. In this study, we initiated a search for genes that are implicated in breast cancer.We analyzed 107 primary patients who were all lymph node negative at the time diagnosis and had experienced relapse. Total RNA isolated from frozen tumor samples was used gather gene expression data using oligo microarrays.A panel 69 found significantly differentially expressed between relapse versus those elsewhere body. most gene, TFF1, confirmed...
Only a subgroup of triple-negative breast cancer (TNBC) responds to immune checkpoint inhibitors (ICI). To better understand lack response ICI, we analyze 681 TNBCs for spatial cell contextures in relation clinical outcomes and pathways T evasion. Excluded, ignored inflamed phenotypes can be captured by gene classifier that predicts prognosis various cancers as well anti-PD1 metastatic TNBC patients phase II trial. The excluded phenotype, which is associated with resistance anti-PD1,...
Abstract Purpose: Molecular characterization of circulating tumor cells (CTC) holds great promise. Unfortunately, routinely isolated CTC fractions currently still contain contaminating leukocytes, which makes CTC-specific molecular extremely challenging. In this study, we determined mRNA and microRNA (miRNA) expression potentially genes that are considered to be clinically relevant in breast cancer. Experimental Design: CTCs were with the epithelial cell adhesion molecule–based CellSearch...
Abstract Introduction Breast cancer is a genetically and phenotypically complex disease. To understand the role of miRNAs in this molecular complexity, we performed miRNA expression analysis cohort molecularly well-characterized human breast cell lines to identify associated with most common subtypes frequent genetic aberrations. Methods Using microarray carrying LNA™ modified oligonucleotide capture probes), levels 725 were measured 51 lines. Differential was explored by unsupervised...
Abstract Purpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head neck) 118 patients. Here, test RSI radiotherapy (RT)-treated breast cancer Experimental Design: tested 2 previously published datasets. Patients were treated at the Karolinska University Hospital (n = 159) Erasmus Medical Center 344). applied as described. Results: We RT-treated patients...
Current normalization methods for RNA-sequencing data allow either intersample comparison to identify differentially expressed (DE) genes or intrasample the discovery and validation of gene signatures. Most studies on optimization typically use simulated validate methodologies. We describe a new method, GeTMM, which allows both inter- analyses with same normalized set. used actual (i.e. not simulated) RNA-seq from 263 colon cancers (no biological replicates) read count compare GeTMM most...
Abstract Background Bone morphogenetic proteins (BMPs) have been reported to maintain epithelial integrity and antagonize the transforming growth factor β (TGFβ)-induced mesenchymal transition. The expression of soluble BMP antagonists is dysregulated in cancers interrupts proper signaling breast cancer. Methods In this study, we mined prognostic role GREMLIN 1 ( GREM1 ) primary cancer tissues using in-house publicly available datasets. We determined which cells express RNA situ...
Tumor cell migration is a key process for cancer dissemination and metastasis that controlled by signal-mediated cytoskeletal matrix adhesion remodeling. Using phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases adhesome- migration-related proteins to identify affect tumor speed persistence. Thirty candidate altered were validated in live assays. Eight associated metastasis-free survival breast patients,...
A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers substitution signatures the transcriptome 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 CDH1. We find CCND3 levels do not correlate with amplification, while increased GATA3 in mutant cancers suggests is an oncogene. In luminal cases total number substitutions, irrespective type,...
Circular RNAs (circRNAs) are a class of that is under increasing scrutiny, although their functional roles debated. We analyzed RNA-seq data 348 primary breast cancers and developed method to identify circRNAs does not rely on unmapped reads or known splice junctions. identified 95,843 circRNAs, which 20,441 were found recurrently. Of the match exon boundaries same gene, 668 showed poor even negative ( R < 0.2) correlation with expression level linear gene. In silico analysis only...
Abstract Genomic rearrangements that give rise to oncogenic gene fusions can offer actionable targets for cancer therapy. Here we present a systematic analysis of among clinically well-characterized, prospectively collected set 278 primary colon cancers spanning diverse tumor stages and clinical outcomes. Gene somatic genetic variations were identified in fresh frozen specimens by Illumina RNA-sequencing, the STAR fusion detection pipeline, GATK RNA-seq variant calling. We considered be...
Abstract Background Published prognostic gene signatures in breast cancer have few genes common. Here we provide a rationale for this observation by studying the power and underlying biological pathways of different signatures. Methods Gene to predict development metastases estrogen receptor-positive receptor-negative tumors were identified using 500 re-sampled training sets mapping Ontology Biological Process identify over-represented pathways. The Global Test program confirmed that...