Melanoma whole exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance

@inproceedings{Shi2012MelanomaWE,
  title={Melanoma whole exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance},
  author={Hubing Shi and Gatien Moriceau and Xiangju Kong and Mi Kyung Lee and Hane Lee and Richard Chikara Koya and Charles P. Ng and Thinle Chodon and Richard A Scolyer and Kimberly Brown Dahlman and Jeffrey A. Sosman and Richard F. Kefford and Georgina V Long and Stanley F. Nelson and Antoni Ribas and Roger S. Lo},
  booktitle={Nature communications},
  year={2012}
}
The development of acquired drug resistance hampers the long-term success of B-RAF inhibitor therapy for melanoma patients. Here we show (V600E)B-RAF copy-number gain as a mechanism of acquired B-RAF inhibitor resistance in 4 out of 20 (20%) patients treated with B-RAF inhibitor. In cell lines, (V600E)B-RAF overexpression and knockdown conferred B-RAF inhibitor resistance and sensitivity, respectively. In (V600E)B-RAF amplification-driven (versus mutant N-RAS-driven) B-RAF inhibitor resistance… CONTINUE READING
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