Publications
Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency Syndrome Vrije Universiteit Brussel
Monoallelic PMS2 germline mutations cause 5%-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA- and RNA-based strategies are applied to overcome problematic PMS2 mutation analysis due to the presence of pseudogenes and frequent gene conversion events. Here, we determined ...
The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth Vrije Universiteit Brussel
Glioblastoma (GBM) is the most aggressive and an incurable type of brain cancer. Human cytomegalovirus (HCMV) DNA and encoded proteins, including the chemokine receptor US28, have been detected in GBM tumors. US28 displays constitutive activity and is able to bind several human chemokines, leading to the activation of various proliferative and inflammatory signaling pathways. Here we show that HCMV, through the expression of US28, ...
No evidence for increased mortality in SDHD variant carriers compared with the general population Vrije Universiteit Brussel
Germline variants in subunit D of the succinate dehydrogenase gene (SDHD variants) are associated with an increased risk of developing paragangliomas. The aim of this study was to compare mortality rates and survival in a Dutch cohort of SDHD variant carriers with those in the general population. The study was conducted at the Leiden University Medical Center, a tertiary referral center for patients with paragangliomas. Included subjects all ...
Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape Vrije Universiteit Brussel
We describe a subset of glioblastoma, the most prevalent malignant adult brain tumour, harbouring a bias towards hypomethylation at defined differentially methylated regions. This epigenetic signature correlates with an enrichment for an astrocytic gene signature, which together with the identification of enriched predicted binding sites of transcription factors known to cause demethylation and to be involved in astrocytic/glial lineage ...
Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer Vrije Universiteit Brussel
Germline variants affecting the exonuclease domains of POLE and POLD1 predispose to multiple colorectal adenomas and/or colorectal cancer (CRC). The aim of this study was to estimate the prevalence of previously described heterozygous germline variants POLE c.1270C>G, p.(Leu424Val) and POLD1 c.1433G>A, p.(Ser478Asn) in a Dutch series of unexplained familial, early onset CRC and polyposis index cases. We examined 1188 familial CRC and ...
Fetal and neonatal neurogenetics Vrije Universiteit Brussel
Disorders of the developing nervous system may be of genetic origin, comprising congenital malformations of spine and brain as well as metabolic or vascular disorders that affect normal brain development. Acquired causes include congenital infections, hypoxic-ischemic or traumatic brain injury, and a number of rare neoplasms. This chapter focuses on the clinical presentation and workup of neurogenetic disorders presenting in the fetal or ...
Genomic Microsatellite Signatures Identify Germline Mismatch Repair Deficiency and Risk of Cancer Onset Vrije Universiteit Brussel
PURPOSE: Diagnosis of Mismatch Repair Deficiency (MMRD) is crucial for tumor management and early detection in patients with the cancer predisposition syndrome constitutional mismatch repair deficiency (CMMRD). Current diagnostic tools are cumbersome and inconsistent both in childhood cancers and in determining germline MMRD.
PATIENTS AND METHODS: We developed and analyzed a functional Low-pass Genomic Instability Characterization ...
Correlation of EGFR, IDH1 and PTEN status with the outcome of patients with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking monoclonal antibody cetuximab Vrije Universiteit Brussel
Mutation and gene amplification of the epithelial growth factor receptor (EGFR) is one of the most common genetic alterations in glioblastoma (GB). EGFR is, therefore, an attractive molecular target for the treatment of GB. EGFR-targeted therapies however have been largely ineffective in clinical trials. In this study, we investigated the correlation between the EGFR gene amplification status, expression of the EGFR variant III (EGFRvIII) and ...
Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR) Vrije Universiteit Brussel
BACKGROUND: Effective treatments are needed to improve outcomes for high-grade glioma and low-grade glioma. The activity and safety of dabrafenib plus trametinib were evaluated in adult patients with recurrent or progressive BRAFV600E mutation-positive high-grade glioma and low-grade glioma.
METHODS: This study is part of an ongoing open-label, single-arm, phase 2 Rare Oncology Agnostic Research (ROAR) basket trial at 27 community and ...