Identification of a MEK2 mutation in a melanoma sample resistant to dabrafenib/trametinib. Identification of a MEK2 mutation in a melanoma sample resistant.

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Identification of a MEK2 mutation in a melanoma sample resistant to dabrafenib/trametinib. Identification of a MEK2 mutation in a melanoma sample resistant to dabrafenib/trametinib. A, WES (left) and RNA-seq (right) of the tumor tissue from patient 1 both before treatment and after the development of resistance to dabrafenib/trametinib revealed a Q60P mutation in MEK2 in the resistant tumor that was undetectable in the pretreatment tumor. B, the fraction of tumor cells (CCF) harboring each alteration was calculated for the pretreatment and resistant tumor samples. Direct comparison of the CCF for all alterations in the pretreatment and resistant tumor samples demonstrated alterations that occurred in the pretreatment sample only (bottom right, blue), the resistant sample only (top left, purple), or both samples (top right, red). Fifteen missense mutations were identified as occurring in the resistant sample only (top left, purple), including the MEK2Q60P mutation (see Supplementary Table S3). Nikhil Wagle et al. Cancer Discovery 2014;4:61-68 ©2014 by American Association for Cancer Research