TY  - JOUR
A1  - Vujanić, Gordan M.
A1  - Gessler, Manfred
A1  - Ooms, Ariadne H. A. G.
A1  - Collini, Paola
A1  - Coulomb-l'Hermine, Aurore
A1  - D'Hooghe, Ellen
A1  - de Krijger, Ronald R.
A1  - Perotti, Daniela
A1  - Pritchard-Jones, Kathy
A1  - Vokuhl, Christian
A1  - van den Heuvel-Eibrink, Marry M.
A1  - Graf, Norbert
T1  - The UMBRELLA SIOP–RTSG 2016 Wilms tumour pathology and molecular biology protocol
JF  - Nature Reviews Urology
N2  - On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP–RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP–RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP–RTSG pathology panel.
KW  - molecular biology
KW  - paediatric cancer
KW  - pathology
KW  - renal cancer
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233265
VL  - 15
ER  - 
TY  - JOUR
A1  - Stefanovic, Sonia
A1  - Barnett, Phil
A1  - van Duijvenboden, Karel
A1  - Weber, David
A1  - Gessler, Manfred
A1  - Christoffels, Vincent M.
T1  - GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development
JF  - Nature Communications
N2  - The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. Here we assess the transcriptional mechanism underlying this localized differentiation process. We show that atrioventricular canal-specific enhancers are GATA-binding site-dependent and act as switches that repress gene activity in the chambers. We find that atrioventricular canal-specific gene loci are enriched in H3K27ac, a marker of active enhancers, in atrioventricular canal tissue and depleted in H3K27ac in chamber tissue. In the atrioventricular canal, Gata4 activates the enhancers in synergy with Bmp2/Smad signalling, leading to H3K27 acetylation. In contrast, in chambers, Gata4 cooperates with pan-cardiac Hdac1 and Hdac2 and chamber-specific Hey1 and Hey2, leading to H3K27 deacetylation and repression. We conclude that atrioventricular canal-specific enhancers are platforms integrating cardiac transcription factors, broadly active histone modification enzymes and localized co-factors to drive atrioventricular canal-specific gene activity.
KW  - biological sciences
KW  - developmental biology
KW  - molecular biology
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121437
SN  - 2041-1723
VL  - 5
IS  - 3680
ER  -