A5041093711- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
- Cancer-related molecular mechanisms research
- Estrogen and related hormone effects
- Breast Cancer Treatment Studies
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Colorectal Cancer Treatments and Studies
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- MicroRNA in disease regulation
- Gene expression and cancer classification
- PARP inhibition in cancer therapy
- Molecular Biology Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Genetics, Bioinformatics, and Biomedical Research
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Protease and Inhibitor Mechanisms
- Cancer Immunotherapy and Biomarkers
Cancer Genomics Centre
2013-2023
Erasmus MC Cancer Institute
2014-2023
Erasmus MC
2014-2023
Erasmus University Rotterdam
2006-2023
Meertens Institute
2007-2023
Codarts Rotterdam
2016
Center for Translational Molecular Medicine
2014-2015
Radboud University Medical Center
2006-2014
Sahlgrenska University Hospital
2014
Radboud University Nijmegen
2006-2014
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...
Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with having dismal survival. We sequenced whole genomes or a panel 365 genes on 299 samples from 170 locally relapsed cancer. Several lines analysis indicate that clones seeding metastasis relapse disseminate late tumors, but continue to acquire mutations, mostly accessing the same mutational processes active tumor. Most distant metastases acquired driver...
The functional roles of SNPs within the 8q24 gene desert in cancer phenotype are not yet well understood. Here, we report that CCAT2 , a novel long noncoding RNA transcript (lncRNA) encompassing rs6983267 SNP, is highly overexpressed microsatellite-stable colorectal and promotes tumor growth, metastasis, chromosomal instability. We demonstrate MYC miR–17–5p, miR–20a up-regulated by through TCF7L2-mediated transcriptional regulation. further identify physical interaction between TCF7L2...
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...
We previously identified in a single-center study 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this was to validate gene an independent more diverse population LNN patients from multiple institutions.Using custom-designed DNA chips we analyzed the expression 76 genes RNA frozen tumor samples 180 who did not receive adjuvant systemic treatment.In validation, highly informative identifying with distant metastasis within 5 years (hazard ratio,...
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...
Abstract Somatic mutations in human cancers show unevenness genomic distribution that correlate with aspects of genome structure and function. These are, however, generated by multiple mutational processes operating through the cellular lineage between fertilized egg cancer cell, each composed specific DNA damage repair components leaving its own characteristic signature on genome. Using somatic mutation catalogues from 560 breast whole-genome sequences, here we 12 base substitution, 2...
Colorectal cancer stem cells (CSCs) express Lgr5 and display extensive cell-like multipotency self-renewal are thought to seed metastatic disease. Here, we used a mouse model of colorectal (CRC) human tumor xenografts investigate the cell origin metastases. We found that most disseminated CRC in circulation were Lgr5− formed distant metastases which Lgr5+ CSCs appeared. This plasticity occurred independently stemness-inducing microenvironmental factors was indispensable for outgrowth, but...
An antiviral enzyme promotes drug resistance in breast cancer.
To discover a set of markers predictive for the type response to endocrine therapy with antiestrogen tamoxifen using gene expression profiling.The study was performed on 112 estrogen receptor-positive primary breast carcinomas from patients advanced disease and clearly defined types (ie, 52 objective v 60 progressive disease) start first-line treatment tamoxifen. Main clinical end points are effects tumor size time until progression (progression-free survival [PFS]). RNA isolated samples...
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...
Article The MTT Tetrazolium Salt Assay Scrutinized: How to Use this Reliably Measure Metabolie Activity of Cell Cultures in vitro for the Assessment Growth Characteristics, IC50-Values and Survival was published on January 1, 1995 journal Clinical Chemistry Laboratory Medicine (CCLM) (volume 33, issue 11).
Abstract Purpose: We previously discovered an extracellular matrix (ECM) gene cluster associated with resistance to first-line tamoxifen therapy of patients metastatic breast cancer. In this study, we determined whether the six individual ECM genes [collagen 1A1 (COL1A1), fibronectin 1 (FN1), lysyl oxidase (LOX), secreted protein acidic cysteine-rich (SPARC), tissue inhibitor metalloproteinase 3 (TIMP3), and tenascin C (TNC)] were treatment response, prognosis, or both. Experimental Design:...
The clinical outcome of BC patients receiving the same treatment is known to vary considerably and thus, there a compelling need identify novel biomarkers that can select would benefit most from given therapy predict outcome. aim this study was determine prognostic value CCAT2, long ncRNA recently characterized by our group overlapping SNP rs6983267, in patients. We first evaluated RT-qPCR ISH expression CCAT2 normal breast tissue further analyzed an independent set 997 primary with regard...
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...
Molecular characterisation of single circulating tumour cells (CTCs) holds considerable promise for predictive biomarker assessment and to explore CTC heterogeneity. We evaluate a new method, the DEPArray system, that allows dielectrophoretic manipulation isolation 100% purified groups CTCs from pre-enriched blood samples feasibility their molecular characterisation. Samples containing known numbers two cell populations were used assess loss during sample loading. Cultured breast cancer...