Fig. 3.
An acquired MEK1 mutation in AZD6244-resistant metastatic melanoma. PCR products corresponding to MEK1 exons 3 and 6 (A) were generated from relapsed melanomas treated with AZD6244; products were pooled and interrogated by massively parallel sequencing (a single Illumina lane). (B) A single mutation, MEK1P124L, was recovered by this analysis. (C) Sanger sequencing chromatograms from MEK1 exon 3 corresponding to pretreatment and postrelapse melanoma DNA from patient 7 are shown. A C > T transition, indicative of MEK1P124L, is evident only in the relapsed sample. (D) Changes in RECIST total count (blue graph) and serum S100 levels (red graph) are plotted over the clinical course of patient 7. The times of pretreatment and postrelapse biopsies are indicated. The intervals of temozolomide treatment (shaded blue) and AZD6244 treatment (shaded pink) are shown.