Manuel Lauinger, Daniel Christen, Rhena F U Klar, Carole Roubaty, Christoph E Heilig, Michael Stumpe, Jennifer J Knox, Nikolina Radulovich, Laura Tamblyn, Irene Y Xie, Peter Horak, Andrea Forschner, Michael Bitzer, Uwe A Wittel, Melanie Boerries, Claudia R Ball, Christoph Heining, Hanno Glimm, Martina Fröhlich, Daniel Hübschmann, Steven Gallinger, Ralph Fritsch, Stefan Fröhling, Grainne M O'Kane, Jörn Dengjel, Tilman Brummer
In-frame BRAF exon 12 deletions are increasingly identified in various tumor types. The resultant BRAFΔβ3-αC oncoproteins usually lack five amino acids in the β3-αC helix linker and sometimes contain de novo insertions. The dimerization status of BRAFΔβ3-αC oncoproteins, their precise pathomechanism, and their direct druggability by RAF inhibitors (RAFi) has been under debate. Here, we functionally characterize BRAFΔLNVTAP>F and two novel mutants, BRAFdelinsFS and BRAFΔLNVT>F , and compare them with other BRAFΔβ3-αC oncoproteins...
September 2023: Science Advances