CENTRUM
KLINISCH LABORATORIUM ARTIKELS ABSTRACT 1 Lethal injection of a castor bean extract: ricinine quantification as a marker for ricin exposure using a validated LC–MS/MS method.
CONCLUSION DMAS-qPCR comes with a complimentary online assay design tool, available for the whole scientific community, enabling researchers to design custom assays and implement those as a diagnostic test.
ABSTRACT 3 Verougstraete N, Helsloot D, Casier I, et al. Journal of Analytical Toxicology, 2019, 43(3), e1-e5
ALK positively regulates MYCN activity through repression of HBP1 expression.
Het abstract is terug te vinden op pagina 7.
Claeys S, Denecker G, Van Maerken T, et al. Oncogene, 2019, 38(15), 2690-2705
ABSTRACT 2
INTRODUCTION/BACKGROUND
Cost-effective and robust genotyping using doublemismatch allele-specific quantitative PCR.
ALK mutations occur in 10% of primary neuroblastomas and represent a major target for precision treatment. In combination with MYCN amplification, ALK mutations infer an ultra-high-risk phenotype resulting in very poor patient prognosis.
Lefever S, Rihani A, Van Maerken T, et al. Scientific Reports, 2019, 9(1), 2150
INTRODUCTION/BACKGROUND
OBJECTIVE
For a wide range of diseases, SNPs in the genome are the underlying mechanism of dysfunction. Therefore, targeted detection of these variations is of high importance for early diagnosis and (familial) screenings. While allele-specific PCR has been around for many years, its adoption for SNP genotyping or somatic mutation detection has been hampered by its low discriminating power and high costs.
To open up opportunities for future precision drugging, a deeper understanding of the molecular consequences of constitutive ALK signaling and its relationship to MYCN activity in this aggressive pediatric tumor entity will be essential.
OBJECTIVE To tackle this, we developed a cost-effective qPCR based method, able to detect SNPs in a robust and specific manner.
MATERIAL/METHODS This study describes how to combine the basic principles of allele-specific PCR (the combination of a wild type and variant primer) with the straightforward readout of DNA-binding dye based qPCR technology. To enhance the robustness and discriminating power, an artificial mismatch in the allele-specific primer was introduced.
RESULTS The resulting method, called double-mismatch allele-specific qPCR (DMAS-qPCR), was successfully validated using 12 SNPs and 15 clinically relevant somatic mutations on 48 cancer cell lines. It is easy to use, does not require labeled probes and is characterized by high analytical sensitivity and specificity.
RESULTS We show that mutant ALK downregulates the 'HMG-box transcription factor 1' (HBP1) through the PI3K-AKT-FOXO3a signaling axis. HBP1 inhibits both the transcriptional activating and repressing activity of MYCN, the latter being mediated through PRC2 activity. HBP1 itself is under negative control of MYCN through miR-17~92. Combined targeting of HBP1 by PI3K antagonists and MYCN signaling by BET- or HDAC-inhibitors blocks MYCN activity and significantly reduces tumor growth, suggesting a novel targeted therapy option for high-risk neuroblastoma.
ABSTRACT 4 Nosocomial outbreak of extended-spectrum β-lactamase-producing Enterobacter cloacae among cardiothoracic surgical patients: causes and consequences. Noël A, Vastrade C, Van Maerken T, et al. Journal of Hospital Infection, 2019, 102(1), 54-60
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