New data, generated by Peter Lichter and colleagues, at the German Cancer Research Center, Heidelberg, have characterized a molecular pathway underlying low-grade forms of a type of brain tumor known as an astrocytoma. The authors therefore suggest that therapeutics targeting this pathway might provide a new approach to treating individuals with low-grade atrocytomas.
Analysis of the DNA of astrocytomas from a large number of children revealed that the most common genetic mutation was the duplication of a region of DNA containing the BRAF gene. Tumors with this genetic mutation showed signs of increased BRAF protein activity. Consistent with the idea that increased BRAF activity had a role in the development of the tumors, mutations in the BRAF gene that caused increased BRAF protein activity were detected in tumors that did not exhibit duplication of the region of DNA containing the BRAF gene. As pharmacologic and genetic silencing of the BRAF signaling pathway and the BRAF gene, respectively, prevented tumor cells from low-grade gliomas growing in culture, it was suggested that inhibiting the signaling pathway downstream of BRAF might be beneficial for individuals with low-grade atrocytomas.
TITLE: BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas
AUTHOR CONTACT:
Peter Lichter
German Cancer Research Center, Heidelberg, Germany.
Phone: 49-6221-424619; Fax: 49-6221-424639; E-mail: m.macleod@dkfz.de .
View the PDF of this article at: https://www.the-jci.org/article.php?id=33656
Journal of Clinical Investigation