C7 - Hepatocellular carcinoma - identification of transforming genes by (insertional) mutagenesis

C7_April 2014

Principal Investigators:
Prof. Dr. rer. nat. Boris Fehse
Forschungsabteilung für Zell- und Gentherapie
Klinik für Stammzelltherapie
Universitätsklinikum Hamburg-Eppendorf
Martinistrasse 52
20246 Hamburg
Tel.: +49-40-7410-55518
Fax: +49-40-7410-55468
E-Mail: fehse@uke.de

PD Dr. Daniel Benten
I. Medizinische Klinik
Universitätsklinikum Hamburg-Eppendorf
Martinistrasse 52
20246 Hamburg
Tel.: +49-40-7410-54240
Fax: +49-40-7410-59092
E-Mail: dbenten@uke.de

Project description

Molecular triggers and mechanisms of liver cancer (hepatocellular carcinoma, HCC) development are still not well understood. It is therefore urgent to follow new paths to facilitate a better understanding of cancerogenesis in the liver.

HCC is the fifth frequent cancer (with increasing incidence) in the world; with regard to cancer-related deaths, it is even on the third place. A better understanding of molecular mechanisms driving HCC could open the pave to develop novel therapeutic strategies.

C7 in 60 SecondsVideoarchiv

online seit 03.12.2012

In the first period of support, we have been able to show that insertional mutagenesis can be used to identify genes playing a causal role in HCC development. In addition, we developed new cell-marking strategies (RGB marking, Barcoding) facilitating qualitative and quantitative analysis of the composition of polyclonal cell structures on a single-cell level.

In the current period, we will be identifying further candidate genes and verify their role in HCC development. In addition, using our innovative marking techniques we will be able to analyse clonal progression during cancerogenesis as well as also normal liver regeneration, e.g. after hepatitis, with very high resolution.

Related news:

Abramowski P, Kraus O, Rohn S, Riecken K, Fehse B, Schlüter H

Combined Application of RGB Marking and Mass Spectrometric Imaging Facilitates Detection of Tumor Heterogeneity
Cancer Genomics Proteomics. 2015 07-08;12(4):179-187.

Cornils K, Thielecke L, Hüser S, Forgber M, Thomaschewski M, Kleist N, Hussein K, Riecken K, Volz T, Gerdes S, Glauche I, Dahl A, Dandri M, Roeder I, Fehse B

Multiplexing clonality: Combining RGB-marking and genetic barcoding
Nucleic Acids Res. 2014 Apr;42(7):e56. doi: 10.1093/nar/gku081. Epub 2014 Jan 29

Heim D, Cornils K, Schulze K, Fehse B, Lohse AW, Brümmendorf AW, Wege H

Retroviral insertional mutagenesis in telomerase-immortalized hepatocytes identifies RIPK4 as novel tumor suppressor in human hepatocarcinogenesis
Oncogene. 2015 Jan 15;34(3):364-72. doi: 10.1038/onc.2013.551. Epub 2014 Jan 13.