Vemurafenib-Resistant PDXs Commonly Display MAPK Pathway Reactivation and Have Distinct Resistance Mechanisms
(A) Immunoblotting of all six matched PDX pairs for factors in the MAPK pathway in pre-vemurafenib and post-relapse PDXs. Asterisks indicate PDXs that were xenografted in mice that received PLX4720 chow.
(B) Copy-number profiles for matched PDX pairs, determined by CopywriteR, are shown.
(C) Amplification of the genomic region containing BRAFT1799A was identified in M009R.X1 (top panel). Validation of this amplification was performed by qPCR on gDNA (bottom panel). CRAF was included as a negative control. CT values were normalized to LINE.
(D) Mutation matrix for matched PDX pairs, comparing pre-vemurafenib and post-relapse tumors. Number of mutations is indicated; each black line represents one mutation.