TY  - JOUR
A1  - Schümann, Franziska Lea
A1  - Groß, Elisabeth
A1  - Bauer, Marcus
A1  - Rohde, Christian
A1  - Sandmann, Sarah
A1  - Terziev, Denis
A1  - Müller, Lutz P.
A1  - Posern, Guido
A1  - Wienke, Andreas
A1  - Fend, Falko
A1  - Hansmann, Martin-Leo
A1  - Klapper, Wolfram
A1  - Rosenwald, Andreas
A1  - Stein, Harald
A1  - Dugas, Martin
A1  - Müller-Tidow, Carsten
A1  - Wickenhauser, Claudia
A1  - Binder, Mascha
A1  - Weber, Thomas
T1  - Divergent effects of EZH1 and EZH2 protein expression on the prognosis of patients with T-cell lymphomas
JF  - Biomedicines
N2  - T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95% confidence interval (CI): 0.044–0.767; p = 0.020;) and EZH2 (HR = 8.245; 95% CI: 1.898–35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients.
KW  - T-cell non-Hodgkin's lymphomas
KW  - PTCL
KW  - epigenetics
KW  - EZH1
KW  - EZH2
KW  - H3K27me3
KW  - immunohistochemistry
KW  - next generation sequencing
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252155
SN  - 2227-9059
VL  - 9
IS  - 12
ER  - 
TY  - JOUR
A1  - Weber, Thomas
A1  - Schmidt, Erwin
A1  - Scheer, Ulrich
T1  - Mapping of transcription units on Xenopus laevis lampbrush chromosomes by in situ hybridization with biotin-labeled cDNA probes
N2  - A non-radioactive in situ hybridization method is described for the localization of transcription units of defined genes to lateral loops of Xenopus laevis lampbrush chromosomes. Two Xenopus cONA probes were used encoding the nucleolar protein N038/ B23 and cytokeratin 1(8). Both proteins are known to be synthesized in Xenopus oocytes, and Northern blot analysis revealed the presence of the corresponding mRNAs in different oogenic stages. The probes were enzymatically labeled with biotin-dCTP and hybridized to lampbrush chromosomes. The sites of hybridization were detected either by indirect immunofluorescence microscopy using rabbit antibodies against biotin and fluorescein-conjugated antirabbit IgG or enzymatically using peroxidase-conjugated streptavi din. The probe encoding the nucleolar protein hybridized to two sets of lateral loops on different bivalents, the cytokeratin probe to at least four. Our finding that each probe hybridized to more than one chromosomal locus may reflect the tetraploid nature of the Xenopus laevis genome or results from cross-hybridization to other transcriptionally active members of the N038/ B23-nucleoplasmin or the cytokeratin-Iamin gene families. The method described should facilitate further in situ hybridization studies with appropriate genomic clones in order to map specific DNA sequences to defined loop regions and to come to a better understanding of the relationship between loop organization and gene transcription unit.
KW  - Cytologie
KW  - Lampbrush chromosomes
KW  - in situ hybridization
KW  - transcription units
KW  - Xenopus oocytes
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-40763
ER  -