Findings May Spur Development of Drugs to Treat Brain Tumors in Infants

Efforts to develop drugs to treat a benign form of pediatric brain tumor may be facilitated by the discovery of a mutation linked to the sporadic development of such tumors.

The growth of benign pilocytic astrocytomas in small children often occurs in the context of neurofibromatosis 1 (NF1), an inherited condition that is one of the most common tumor predisposition syndromes, as well as arising spontaneously without connection to NF1. Conditions caused by these tumors include headache, nausea, vomiting, problems with balance, and visual impairment.


Investigators at the Washington University School of Medicine (St. Louis, MO, USA) performed detailed genetic and genomic analyses of tumor samples from 70 patients with sporadic pilocytic astrocytomas and nine patients with NF1. They reported in the September 30, 2009, online edition of the journal Neurology that 42 of the 70 patients with sporadic pilocytic astrocytomas had alterations in the BRAF gene, while none of the NF1 patients did.

The protein encoded by the BRAF gene plays a role in regulating the MAP kinase/ERKs signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene have been associated with various cancers, including non-Hodgkin lymphoma, colorectal cancer, malignant melanoma, thyroid carcinoma, non-small-cell lung carcinoma, and lung adenocarcinoma.

"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," explained senior author Dr. David H. Gutmann, professor of neurology at the Washington University School of Medicine. "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. 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 is important because right now we have few treatments tailored to this tumor type."

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Washington University School of Medicine