Washington University LogoResearchers at Washington University School of Medicine in St. Louis are believed to have linked mutations in a gene to a benign pediatric brain tumor. Apparently, this finding may assist scientists in looking for drug treatments that block the growth of the tumors.

David Gutmann normally seems to have examined the tumors, known as pilocytic astrocytomas, in the context of neurofibromatosis 1 (NF1). NF1 is known to be an inherited condition that is one of the most common tumor predisposition syndromes.

However, pilocytic astrocytomas could perhaps also occur intermittently in patients who do not have the NF1 mutation at a rate of about 2-3 novel cases per 100,000 children per year. Apparently, symptoms from these tumors can include headache, nausea, vomiting, problems with balance and visual impairment.

David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology said that, “Now that we understand the signature mutation in these common pediatric tumors, we can think about designing treatments that alter the pathway that gene controls. That’s important because right now we have few treatments tailored to this tumor type.”

In order to discover whether either condition could shed light on the other, Gutmann’s team appears to have performed complete genetic and genomic analyses of tumor samples from approximately 70 patients with sporadic pilocytic astrocytomas and nine patients with NF1.

A previous lead linking the sporadic tumors to changes in a gene called HIPK2 in a small region of chromosome 7 may have been unable to criticize out. However, it seems to have led the researchers to the nearby BRAF gene, which was earlier linked to other cancers.

“BRAF was a particularly enticing target because the signaling pathway that it controls is also controlled by neurofibromin, the protein made by the gene that is mutated in patients with NF1. This finding is exciting, since a number of drugs are known to inhibit this pathway, some of which are already being tested for their ability to control the growth of other cancers,” says Gutmann, who is director of the Washington University Neurofibromatosis Center.

The findings of the research revealed that nearly 42 of the 70 patients with sporadic pilocytic astrocytomas appear to have alterations in the BRAF gene, whereas none of the NF1 patients did. Further research revealed that the second half of the altered BRAF protein could possibly combine to another gene in the same region of chromosome 7. Supposedly, BRAF normally regulates cell growth. However, when its protein combines with the other gene, BRAF seems to become overactive thereby causing increased growth that culminates in astrocytoma development.

Besides, standard chemotherapy, there appear to be no treatments at present that target the specific molecular alterations in pilocytic astrocytoma. Surgery may possibly be used sometimes to remove the tumors, but they often occur in surgically remote regions of the brain like the optic nerve and brainstem. Furthermore, radiation treatment could result into long-term cognitive deficits.

In order to further understand how BRAF is linked to cell growth, Gutmann and his colleagues are observed to be working to create a model of sporadic low-grade astrocytoma in mice. Additionally, they seem to be finding out exactly how BRAF regulates cell growth. Their group previously was noted to have developed a mouse model of NF1-associated optic glioma.

The findings of the research have been published in the journal, Neurology.