Cookie Settings

We use cookies to optimize our website. These include cookies that are necessary for the operation of the site, as well as those that are only used for anonymous statistic. You can decide for yourself which categories you want to allow. Further information can be found in our data privacy protection .


These cookies are necessary to run the core functionalities of this website and cannot be disabled.

Name Webedition CMS
Purpose This cookie is required by the CMS (Content Management System) Webedition for the system to function correctly. Typically, this cookie is deleted when the browser is closed.
Name econda
Purpose Session cookie emos_jcsid for the web analysis software econda. This runs in the “anonymized measurement” mode. There is no personal reference. As soon as the user leaves the site, tracking is ended and all data in the browser are automatically deleted.

These cookies help us understand how visitors interact with our website by collecting and analyzing information anonymously. Depending on the tool, one or more cookies are set by the provider.

Name econda
Purpose Statistics
External media

Content from external media platforms is blocked by default. If cookies from external media are accepted, access to this content no longer requires manual consent.

Name YouTube
Purpose Show YouTube content
Name Twitter
Purpose activate Twitter Feeds

Altered DNA methylation as a warning sign of radiation-induced fibrosis

No. 15 | 18/03/2016 | by Koh

Radiation-induced fibrosis is a common late effect of radiation therapy. In a study on breast cancer, scientists from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and Mannheim University Hospital have now identified an epigenetic pattern that indicates an increased risk of fibrosis. In the future, this epigenetic characteristic might be used before starting radiation therapy as a biomarker indicating whether a patient is highly susceptible to fibrosis. Its effect is that skin cells increase the production of an enzyme that induces the development of fibrosis. Specific agents might interrupt this process.

© Christoph Bock/Wikimedia Commons

Since medical technology has enabled physicians to irradiate tumors ever more precisely, radiation therapy has become part of the treatment regimen for about two thirds of cancer patients. Radiotherapy is well tolerated in most cases, but patients may also develop side effects. One debilitating side effect is radiation-induced fibrosis, which can lead to a significant deterioration in the quality of life.

Radiation-induced fibrosis can develop, for example, in the wake of radiation therapy to tumors of the urinary bladder or the lungs. In the case of breast cancer, up to five percent of patients are affected by fibrosis. “If physicians could tell already at the time of diagnosis whether a patient has a particularly high risk of fibrosis, radiation doses could be reduced or other treatment options be chosen,” says Odilia Popanda from the DKFZ.

Fibrosis is a process of scarring by which healthy tissue is replaced by less elastic connective tissue, which leads to hardening and functional impairments. Radiation-induced fibrosis often occurs as a late effect several months or even years after the treatment. Unlike temporary side effects such as fatigue or diarrhea, fibrosis is an irreversible process.

Scientists know only a few genetic markers that are linked to increased susceptibility to fibrosis. These, however, are no satisfactory explanation why this condition is so common in cancer patients. Popanda and colleagues have now investigated evidence suggesting that certain epigenetic features might deregulate cellular signaling pathways that are key to the development of fibrosis.

“We were particularly interested if we could identify epigenetic variations indicating a high fibrosis risk prior to starting radiation therapy,” Popanda explains. To this end, the team isolated connective tissue cells from skin biopsies that had been obtained from 75 breast cancer patients prior to radiotherapy. The researchers investigated the DNA of the cells by conducting a genome-wide analysis of its methylation patterns. 

The investigators found a particularly significant correlation with later development of radiation-induced fibrosis in the genetic enhancer element of an enzyme called DGKA (diacylglycerol kinase alpha). Patients whose DGKA enhancer exhibited only low numbers of methyl groups later turned out to be highly susceptible to fibrosis. Christof Weigel, who is the first author of the publication, summarizes the complex cascade: “If this gene enhancer carries only few methyl labels, certain transcription factors can attach here and the DGKA gene is transcribed more frequently, which eventually leads to the activation of connective tissue cells.”

When the researchers treated skin cells in the Petri dish with an agent that specifically inhibits the DGKA enzyme, the level of activation of connective tissue cells, which is assumed to be a critical first step in fibrosis, was lower.

Popanda and her colleagues are pleased to have not only found a marker indicating a patient’s fibrosis risk, but potentially also a way to prevent this debilitating side effect. DGKA inhibitors have already successfully been used to reduce cancer cell growth and to fight inflammatory processes. Therefore, they might also be used to prevent the development of radiation-induced fibrosis.

Christoph Weigel, Marlon R. Veldwijk, Christopher C. Oakes, Petra Seibold, Alla Slynko, David B. Liesenfeld, Mariona Rabionet, Sabrina A. Hanke, Frederik Wenz, Elena Sperk, Axel Benner, Christoph Rösli, Roger Sandhoff, Yassen Assenov, Christoph Plass, Carsten Herskind, Jenny Chang-Claude, Peter Schmezer & Odilia Popanda: Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis.
Nature Communications 2016, 10.1038/ncomms10893 

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.


Subscribe to our RSS-Feed.

to top
powered by webEdition CMS