Article
Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma.
Cell reports - 26 Sept 2013
Villanueva Jessie, Infante Jeffrey R, Krepler Clemens, Reyes-Uribe Patricia, Samanta Minu, Chen Hsin-Yi, Li Bin, Swoboda Rolf K, Wilson Melissa, Vultur Adina, Fukunaba-Kalabis Mizuho, Wubbenhorst Bradley, Chen Thomas Y, Liu Qin, Sproesser Katrin, DeMarini Douglas J, Gilmer Tona M, Martin Anne-Marie, Marmorstein Ronen, Schultz David C, Speicher David W, Karakousis Giorgos C, Xu Wei, Amaravadi Ravi K, Xu Xiaowei, Schuchter Lynn M, Herlyn Meenhard, Nathanson Katherine L
Abstract excerpt
Although BRAF and MEK inhibitors have proven clinical benefits in melanoma, most patients develop resistance. We report a de novo MEK2-Q60P mutation and BRAF gain in a melanoma from a patient who progressed on the MEK inhibitor trametinib and did not respond to the BRAF inhibitor dabrafenib. We also identified the same MEK2-Q60P mutation along with BRAF amplification in a xenograft tumor derived from a second...
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