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Suspicions confirmed: Brain tumors in children have a common cause
Date:7/9/2013

ered 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."


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Contact: Dr. Sibylle Kohlstädt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

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