Functional characterization of a BRAF insertion mutant associated with pilocytic astrocytoma
28.12.2010
Eisenhardt AE, Olbrich H, Röring M, Janzarik W, Van Anh TN, Cin H, Remke M, Witt H, Korshunov A, Pfister SM, Omran H, Brummer T.
Int J Cancer. 2011, 129(9):2297-2303
Pilocytic astrocytoma (PA), the most common brain tumour in children and young adults, is emerging as a tumor entity with dysregulated Raf signaling. Here, we report and provide the functional characterisation of a novel, PA-associated B-Raf insertion mutant in which T599, a key phosphorylation site within the activation segment, has been duplicated. Our data suggest that the distortion of the activation segment by additional amino acids destabilises the inactive conformation of the kinase domain and thereby confers transforming properties.
