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

Gene fusion opens up treatment possibilities for aggressive brain cancer

No. 43c | 17/10/2016 | by Koh

Glioblastoma, an extremely aggressive type of brain cancer, is still mostly untreatable in children. Scientists from the German Cancer Research Center (DKFZ), Heidelberg University Hospital and an international consortium including the Max Planck Institute for Molecular Genetics (MPIMG) undertook a comprehensive analysis of glioblastoma genomes. In about ten percent of the cases, they found a previously unknown mutation that is treatable with a targeted drug that has already been approved. In experiments with mice, the investigators successfully used this agent to halt the growth of brain tumors with this mutation.


Glioblastoma is one of the most dangerous and aggressive types of brain cancer. Although it occurs mostly in adults, each year approximately 60 children and adolescents in Germany are also diagnosed with this dreaded form of cancer. Established radiotherapy and chemotherapy treatments can usually only slightly delay the progression of the disease. Scientists are therefore urgently searching the genomes of glioblastoma cells for cancer-promoting alterations that can be attacked with modern targeted drugs.

David Jones and his colleagues at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg analyzed the genomes in more than 50 cases of pediatric glioblastoma, in a study published in Nature Medicine. The study was conducted within the German PedBrain Tumor Research Project, which is part of the International Cancer Genome Consortium (ICGC) and focuses on pediatric brain tumors. The researchers identified a large variety of defects that cause the cells to turn cancerous. In ten percent of the cases, which is a remarkable rate, they discovered a defect where a known cancer gene called MET was fused with other DNA segments.

"Fusions of growth-promoting genes are typical for cancer," said Marie-Laure Yaspo from the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin, whose group confirmed the gene fusion discovery. "The most well-known is the so-called 'Philadelphia' chromosome, or BCR-ABL fusion, which is the cause of almost all cases of chronic myeloid leukemia." These gene fusions lead to cancer when a growth-promoting gene that is normally under strict control fuses with other genes that lead to abnormal activation.

MET genes that have undergone mutations or amplification have been described as tumor promoters in other cancer types. MET is one of the receptor proteins in the cell membrane that respond to growth factors. Many of these receptors, including MET, can now be blocked using inhibitors that have been approved as drugs. "In order to be able to treat affected children with these substances, we first needed to prove that MET fusion genes in fact promote the development of glioblastoma," Jones said.

To provide this proof, the investigators transferred MET fusion genes to the respective brain cells in mice. The transferred genes subsequently caused exactly this type of brain cancer – glioblastoma. In further experiments with these animals, the researchers were able to confirm that MET inhibitors significantly slowed down cancer growth.

Children with relapsing cancer mostly have a very small chance of being permanently cured. To improve the curative prospects for these young patients, Heidelberg pediatric oncologists and molecular biologists are coordinating a registry study called INFORM that pursues molecular analysis of tumor genomes. The INFORM project is being carried out within the framework of the German Cancer Consortium (DKTK). In an eight year-old INFORM patient who suffered from glioblastoma, the genome analysis had detected a MET fusion gene. As part of a personalized therapy approach, the physicians treated the child with a MET inhibitor called crizotinib. As a result, the tumor shrunk substantially and the severe disease symptoms improved. At the same time, however, further tumors rapidly formed in the patient's brain which failed to respond to the treatment.

"The drug was effective, but unfortunately it was insufficient," said Stefan Pfister, a pediatric oncologist and molecular biologist at the DKFZ and Heidelberg University Hospital. "Resistance against MET inhibitors is a known problem. It is becoming increasingly clear to us that we have to combine these drugs with other agents." In addition, the MET fusion genes were not the only molecular culprits driving cancer growth. In all tumors, the researchers had also found mutations in genes that control the cell cycle. "It would surely be useful to combine MET inhibitors with agents that normalize the deregulated cell cycle," Pfister said.

The PedBrainTumor Project has been supported by the Federal Ministry of Education and Research (BMBF) and German Cancer Aid (Deutsche Krebshilfe).

Sebastian Bender, Jan Gronych, Hans-Jörg Warnatz, Barbara Hutter, Susanne Gröbner, Marina Ryzhova, Elke Pfaff, Volker Hovestadt, Florian Weinberg, Sebastian Halbach, Marcel Kool, Paul A. Northcott, Dominik Sturm, Lynn Bjerke, Thomas Zichner, Adrian M. Stütz, Kathrin Schramm, Bingding Huang, Ivo Buchhalter, Michael Heinold, Thomas Risch, Barbara Worst, Cornelis M. van Tilburg, Ursula D. Weber, Marc Zapatka, Benjamin Raeder, David Milford, Sabine Heiland, Christof von Kalle, Christopher Previti, Chris Lawerenz, Andreas E. Kulozik, Andreas Unterberg, Olaf Witt, Andreas von Deimling, David Capper, Nathalène Truffaux, Jacques Grill, Nada Jabado, Astrid M. Sehested, David Sumerauer, Dorra Hmida-Ben Brahim, Saoussen Trabelsi, Ho-Keung Ng, David Zagzag, Jeffrey Allen, Matthias A. Karajannis, Nick Gottardo, Chris Jones, Jan O. Korbel, Sabine Schmidt, Stephan Wolf, Guido Reifenberger, Jörg Felsberg, Benedikt Brors, Christel Herold-Mende, Hans Lehrach, Tilman Brummer, Andrey Korshunov, Roland Eils, Marie-Laure Yaspo, Stefan M. Pfister, Peter Lichter, and David T.W. Jones for the International Cancer Genome Consortium PedBrain Tumor Project36: Recurrent MET fusion genes represent a druggable target in paediatric glioblastoma.

Nature Medicine 2016, DOI: 10.1038/nm.4204.

About the INFORM registry:

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