Filter and export

Publications

What is a Publication?
2 Publications matching the given criteria: (Clear all filters)
Author: Mario Brosch2
Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control

Abstract (Expand)

A deeper epigenomic understanding of spatial organization of cells in human tissues is an important challenge. Here we report the first combined positional analysis of transcriptomes and methylomes … across three micro-dissected zones (pericentral, intermediate and periportal) of human liver. We identify pronounced anti-correlated transcriptional and methylation gradients including a core of 271 genes controlling zonated metabolic and morphogen networks and observe a prominent porto-central gradient of DNA methylation at binding sites of 46 transcription factors. The gradient includes an epigenetic and transcriptional Wnt signature supporting the concept of a pericentral hepatocyte regeneration pathway under steady-state conditions. While donors with non-alcoholic fatty liver disease show consistent gene expression differences corresponding to the severity of the disease across all zones, the relative zonated gene expression and DNA methylation patterns remain unchanged. Overall our data provide a wealth of new positional insights into zonal networks controlled by epigenetic and transcriptional gradients in human liver.

Authors: Mario Brosch, Kathrin Kattler, Alexander Herrmann, Witigo von Schönfels, Karl Nordström, Daniel Seehofer, Georg Damm, Thomas Becker, Sebastian Zeissig, Sophie Nehring, Fabian Reichel, Vincent Moser, Raghavan Veera Thangapandi, Felix Stickel, Gustavo Baretton, Christoph Röcken, Michael Muders, Madlen Matz-Soja, Michael Krawczak, Gilles Gasparoni, Hella Hartmann, Andreas Dahl, Clemens Schafmayer, Jörn Walter, Jochen Hampe

Date Published: 1st Dec 2018

Publication Type: Not specified

Evolutionary Distance Predicts Recurrence After Liver Transplantation in Multifocal Hepatocellular Carcinoma.

Abstract (Expand)

BACKGROUND: Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may … be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC. METHODS: In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping. RESULTS: Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 x 10) and microvascular invasion (P = 1.31 x 10) were significantly associated with survival in a Cox regression analysis. CONCLUSIONS: Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered.

Authors: N. Heits, M. Brosch, A. Herrmann, R. Behrens, C. Rocken, H. Schrem, A. Kaltenborn, J. Klempnauer, H. H. Kreipe, B. Reichert, C. Lenschow, C. Wilms, T. Vogel, H. Wolters, E. Wardelmann, D. Seehofer, S. Buch, S. Zeissig, S. Pannach, N. Raschzok, M. Dietel, W. von Schoenfels, S. Hinz, A. Teufel, M. Evert, A. Franke, T. Becker, F. Braun, J. Hampe, C. Schafmayer

Date Published: 12th Jul 2018

Publication Type: Not specified

Powered by
 (v.1.16.1)
About FAIRDOM | About LiSyM | Funding and Programmes | Credits | Terms & Conditions | Imprint
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH