Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Suspicions Confirmed: Common Cause for Brain Tumors in Children

Published: Tuesday, July 09, 2013
Last Updated: Tuesday, July 09, 2013
Bookmark and Share
An overactive signaling pathway is a common cause in cases of pilocytic astrocytoma, the most frequent type of brain cancer in children.

This was discovered by a network of scientists coordinated by the German Cancer Research Center (as part of the International Cancer Genome Consortium, ICGC). In all 96 cases studied, the researchers found defects in genes involved in a particular pathway. Hence, drugs can be used to help affected children by blocking components of the signaling cascade. The project is funded by the German Cancer Aid (Deutsche Krebshilfe) and the Federal Ministry of Education and Research (BMBF). The findings are published in the latest issue of the journal “Nature Genetics”.

Brain cancer is the primary cause of cancer mortality in children. Even in cases when the cancer is cured, young patients suffer from the stress of a treatment that can be harmful to the developing brain. In a search for new target structures that would create more gentle treatments, cancer researchers are systematically analyzing all alterations in the genetic material of these tumors. This is the mission of the PedBrain consortium, which was launched in 2010. Led by Professor Stefan Pfister from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), the PedBrain researchers have now published the results of the first 96 genome analyses of pilocytic astrocytomas.

Pilocytic astrocytomas are the most common childhood brain tumors. These tumors usually grow very slowly. However, they are often difficult to access by surgery and cannot be completely removed, which means that they can recur. The disease may thus become chronic and have debilitating effects for affected children.

In previous work, teams of researchers led by Professor Dr. Stefan Pfister and Dr. David Jones had already discovered characteristic mutations in a major proportion of pilocytic astrocytomas. All of the changes involved a key cellular signaling pathway known as the MAPK signaling cascade. MAPK is an abbreviation for “mitogen-activated protein kinase.” This signaling pathway comprises a cascade of phosphate group additions (phosphorylation) from one protein to the next – a universal method used by cells to transfer messages to the nucleus. MAPK signaling regulates numerous basic biological processes such as embryonic development and differentiation and the growth and death of cells.

“A couple of years ago, we had already hypothesized that pilocytic astrocytomas generally arise from a defective activation of MAPK signaling,” says David Jones, first author of the publication. “However, in about one fifth of the cases we had not initially discovered these mutations. In a whole-genome analysis of 96 tumors we have now discovered activating defects in three other genes involved in the MAPK signaling pathway that have not previously been described in astrocytoma."

“Aside from MAPK mutations, we do not find any other frequent mutations that could promote cancer growth in the tumors. This is a very clear indication that overactive MAPK signals are necessary for a pilocytic astrocytoma to develop,” says study director Stefan Pfister. The disease thus is a prototype for rare cancers that are based on defects in a single biological signaling process.

In total, the genomes of pilocytic astrocytomas contain far fewer mutations than are found, for example, in medulloblastomas, a much more malignant pediatric brain tumor. This finding is in accordance with the more benign growth behavior of astrocytomas. The number of mutations increases with the age of the affected individuals.

About one half of pilocytic astrocytomas develop in the cerebellum, the other 50 percent in various other brain regions. Cerebellar astrocytomas are genetically even more homogenous than other cases of the disease: In 48 out of 49 cases that were studied, the researchers found fusions between the BRAF gene, a central component of the MAPK signaling pathway, and various other fusion partners.

“The most important conclusion from our results,” says study director Stefan Pfister, “is that targeted agents for all pilocytic astrocytomas are potentially available to block an overactive MAPK signaling cascade at various points. We might thus in the future be able to also help children whose tumors are difficult to access by surgery.”

International collaboration in tumor genome analysis

The International Cancer Genome Consortium (ICGC), a network of scientists from currently 15 countries, aims to obtain a comprehensive description of genomic and epigenomic changes in all significant types of cancer. Germany takes part with the PedBrain Tumor Project to analyze pediatric brain tumors (medulloblastoma, which in Germany affects approximately 100 children each year; and pilocytic astrocytoma, which is diagnosed in approximately 200 children each year). Within the PedBrain Tumor Project, 300 samples of each tumor type will be analyzed, along with the same number of samples of healthy tissue from the same patients, to identify changes that are cancer-specific.

The PedBrain Tumor network consists of researchers from seven institutes led by project coordinator Peter Lichter of DKFZ. Alongside the DKFZ, participating project partners in Heidelberg are: the National Center for Tumor Diseases (NCT), Heidelberg University and the University Hospital, and the European Molecular Biology Laboratory (EMBL). In addition, scientists from Düsseldorf University Hospital and the Max Planck Institute for Molecular Genetics in Berlin have taken on tasks in the network project.

The German Cancer Aid (Deutsche Krebshilfe) provided funds of eight million Euros for PedBrain Tumor. Since July 1, 2012, the project has received another seven million Euros from the Federal Ministry of Education and Research (BMBF).

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,600+ scientific posters on ePosters
  • More Than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Lemon Juice and Human Norovirus
Citric acid may prevent the highly contagious norovirus from infecting humans, scientists discovered from the German Cancer Research Center.
Thursday, August 27, 2015
A Yardstick to Measure the Malignancy of Prostate Cancer
Researchers have been searching for regulatory proteins that change the epigenetic characteristics of prostate cancer cells.
Wednesday, December 10, 2014
Blocking Cancer Stem Cells in the Brain Prolongs Survival in Mice
Blocking the stem cell marker slow down the growth of aggressive human brain cancers.
Tuesday, May 27, 2014
Life Technologies Partners with German Cancer Research Center to Create World-Class Genome Sequencing Facility
Life Technologies Corporation and the German Cancer Research Center (Deutsches Krebsforschungszentrum or DKFZ), today announced their collaboration to create the National High-Throughput Sequencing Center.
Thursday, June 03, 2010
Scientific News
13 Ways to Stop an Unseen Force from Disrupting Weighing
Download a free Mettler Toledo paper to discover how to halt static’s negative effects before the next weigh-in.
Flinders Ig Nobel Winner Cracks Global Anaesthetic
One of the world’s most in-demand anaesthetics can now be produced on the spot, thanks to the thermos-flask sized device that recently won Flinders University inventor Professor Colin Raston an Ig Nobel prize.
Resurrected Proteins Double Their Natural Activity
Researchers demonstrate method for reviving denatured proteins.
Genes That Protect African Children From Developing Malaria Identified
Variations in DNA at a specific location on the genome that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the life-threatening disease, have been identified in the largest genetic association study of malaria to date.
Messing With The Monsoon
Manmade aerosols can alter rainfall in the world’s most populous region.
Potential Target for Treatment of Autism
Grant of $2.4 million will support further research.
Scientists Decode Structure at Root of Muscular Disease
Researchers at Rice University and Baylor College of Medicine have unlocked the structural details of a protein seen as key to treating a neuromuscular disease.
Sniffing Out Cancer
Scientists have been exploring new ways to “smell” signs of cancer by analyzing what’s in patients’ breath.
New Test Detects All Viruses
A new test detects virtually any virus that infects people and animals, according to research at Washington University School of Medicine in St. Louis, where the technology was developed.
Inroads Against Leukemia
Potential for halting disease in molecule isolated from sea sponges.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos