How common are brain tumors in teenagers

Understanding the causes of childhood brain tumors - Interview with Dr. Ursula Weber to the International Cancer Genome Consortium

Dr. Ursula Weber, project manager of the PedBrainTumor project at the German Cancer Research Center Heidelberg Germany is also involved - a project is investigating the causes of childhood brain tumors. Dr. Ursula Weber from the German Cancer Research Center in Heidelberg explains in an interview what goals are being pursued and what the first results are.

Miss Dr. Weber, you are investigating the genetic causes of brain tumors in children. Why is that useful?

Not all cancer is alike, and tumors in the same organs can differ greatly from patient to patient. This also applies to brain tumors in children. Even with cancers in which the tumor cells do not seem to differ under the microscope, some patients respond very well to certain therapies, while other patients do not. This suggests that the spread and development of cancer are often individually dependent on the genetic makeup of the tumor. It is therefore important to genetically characterize the tumors precisely.

What exactly are you investigating?

The aim of the PedBrainTumor project is to decode 500 tissue samples from childhood brain tumors using the latest sequencing methods. We use what is known as “next-generation sequencing”, also known as high-throughput sequencing, in which an entire human genome can be completely sequenced, i.e. decoded, within two weeks. The aim of the project is to record all mutations, i.e. changes in the genome, as well as all changes in the activity of genes and in epigenetic information. The latter control the use of DNA and determine which genes are switched on and off exactly when and where. At the same time, we are also examining 500 samples of healthy tissue from tumor patients in order to be able to precisely compare which genetic changes are unique to the tumor. The entirety of this information is intended to contribute to obtaining fundamental knowledge about the development of pediatric brain tumors, to better understanding the tumor biology and ultimately to developing new targeted therapies on the basis of this knowledge.

New therapies are probably urgently needed, especially for childhood brain tumors?

Yes, we urgently need new, targeted and gentle therapy methods. Pediatric brain tumors are the most common childhood cancer and have a fatal outcome. The treatment of the tumors and the associated side effects are often very stressful for the children and can impair the development of the growing brain. We limit our investigations to the two most common childhood brain tumors, medulloblastoma and pilocytic astrocytoma. In Germany around 300 children are affected by these brain tumors every year.

Magnetic resonance imaging (left, the arrow points to the tumor) and tissue section
(right) of a medulloblastoma

What could the decoding of tumor genomes contribute to improved therapy?

Genetic changes can, for example, provide information about the cause of the tumors and serve as target structures for new, personalized therapeutic approaches. At the same time, we want to divide the tumors into subgroups based on their genetics. In the future, the aim is to precisely identify those patients who will benefit from a certain therapy, for example chemotherapy. Because, as I said at the beginning, many tumors cannot be distinguished under the microscope. Genetically, however, they differ considerably. And the choice of therapy can also depend on this.

Have you already had results?

The sequencing of 125 medulloblastomas has already contributed to a significantly better division of the tumors into subgroups than was previously possible. An interesting result is that pediatric medulloblastomas - although they are highly aggressive tumors - carry significantly fewer mutations than all adult tumors that have been investigated so far. A common mutation that we found in another pediatric brain tumor, glioblastoma, is in a gene that is responsible for packaging DNA and thus determining the activity of genes. More precisely, it is the histone modification H3.3 gene. It is therefore clear: in childhood brain tumors, epigenetic factors that control the use of DNA are also changed by mutation.

How are things going now?

In the next few years we will analyze the remaining 250 tumor samples and as many controls as planned. We will validate new findings and transfer frequently found special changes to animal models in order to carry out the preclinical testing of new clinical therapies. All the data collected will be combined in a large database within the framework of the International Cancer Genome Consortium and made available to the international research community.

A scientist from the ICGC recently received the German Cancer Prize.

Exactly. The Heidelberg molecular biologist and pediatrician Professor Dr. Stefan Pfister was honored for his research on the molecular properties of malignant brain tumors in children. With this award, the German Cancer Society honored his achievements in translational cancer research. Translational research in medicine is about the early transfer of fundamental research knowledge into therapeutic application.

ICGC - global networking in the fight against cancer In the International Cancer Genome Consortium (ICGC), scientists around the world are working to genetically examine the 50 most common cancers in order to find new and improved approaches to prevention, diagnosis and therapy. There are currently three German ICGC participations, one is the PedBrainTumor project, which is funded by the Federal Ministry of Education and Research (BMBF) and the German Cancer Aid with a total budget of 15 million euros over a period of five years. The other two projects investigate the molecular causes of malignant lymphomas and early onset prostate cancer. Read more about the ICGC and the German participations here.

Contact person:
Dr. Ursula Weber
German Cancer Research Center Heidelberg (DKFZ)
Molecular Genetics Department
In Neuenheimer Feld 280
69120 Heidelberg
Tel .: 06221 42-4620
Fax: 06221 42-4639
Email: [email protected]