Article Figures & Data
Figures
- Figure 1.
L576P KIT mutation in a melanoma cell line. A, mass spectroscopy-based detection of the L576P KIT mutant allele(s) in the WM3211 cell line. A peak is correlated with the L576P mutant KIT (Mut), whereas there is no peak for the wild-type KIT (WT). B, sanger sequencing of exon 11 of KIT in the WM3211 cells. Arrow, T-to-C base pair change.
- Figure 2.
Effect of KIT inhibitors on WM3211 cell line viability. WM3211 (♦), MEWO (▪), and A375 (▴) human melanoma cells were treated with increasing doses of the KIT inhibitors, A, imatinib, B, sorafenib, C, nilotinib, or D, dasatinib, x-axis, drug concentration (nM); y-axis, percent reduction in cell viability. Each data point represents the average of three replicates, error bars represent the standard deviation.
- Figure 3.
Effects of L576P KIT mutation on protein structure and drug binding. The interaction of imatinib with A, wild-type versus B, L576P KIT reveals a ΔΔGbind = −2.52 kcal/mol, reflecting a decrease in affinity induced by the mutation. The interaction of dasatinib with C, wild-type versus D, L576P KIT reveals a ΔΔGbind = +0.32 kcal/mol. The free binding energy for L576P KIT is more favorable for dasatinib (−9.93 kcal/mole) than for imatinib (−7.75 kcal/mole), indicating a greater affinity for dasatinib.
- Figure 4.
Treatment of L576P KIT mucosal melanoma patients with dasatinib. FDG-PET/CT images of Patient A, A and B, and Patient B, C–F, metastatic mucosal melanoma patients, with L576P KIT mutant tumors. Images were obtained before, A, C, E, and after, B, D, F, treatment with 70 mg twice daily of dasatinib for 1 mo. Solid block white arrows indicate FDG-avid tumors; narrow white arrows indicate physiologic FDG excretion in renal collecting system.
Additional Files
Supplementary Data, Woodman, et al.
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Volume 8, Issue 8
