Scientists have found that an overactive signalling pathway is a common cause in cases of pilocytic astrocytoma,the most frequent type of brain cancer in children.
Scientists coordinated by the German Cancer Research Center (as part of the International Cancer Genome Consortium,ICGC) in 96 gemone analyses of pilocytic astrocytomas found defects in genes involved in a particular pathway.
They believe that drugs can be used to help affected children by blocking components of the signalling cascade. Pilocytic astrocytomas are the most common childhood brain tumours. These tumours usually grow very slowly. However,they are often difficult to access by surgery and cannot be completely removed,which means that they can recur.
In previous work,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 signalling pathway known as the MAPK signalling cascade. MAPK is an abbreviation for ‘mitogen-activated protein kinase’.
This signalling 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 signalling 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 hypothesised that pilocytic astrocytomas generally arise from a defective activation of MAPK signalling,” said Jones,first author of the study in journal Nature Genetics.
“However,in about one fifth of the cases we had not initially discovered these mutations. In a whole-genome analysis of 96 tumours we have now discovered activating defects in three other genes involved in the MAPK signalling pathway that have not previously been described in astrocytoma,” he said.
“Aside from MAPK mutations,we do not find any other frequent mutations that could promote cancer growth in the tumours. This is a very clear indication that overactive MAPK signals are necessary for a pilocytic astrocytoma to develop,” said study director Pfister.
“The most important conclusion from our results is that targeted agents for all pilocytic astrocytomas are potentially available to block an overactive MAPK signalling cascade at various points,” said Pfister. “We might thus in the future be able to also help children whose tumours are difficult to access by surgery,” he said.