Tumors from KitV558Δ;Y567F/Y567F mice are smaller and have lower MAPK and SFK pathway activation than tumors from KitV558Δ/+ mice. (A) Representative gross cecal GISTs from 3-mo-old mice. (B) H&E staining of cross-sections of cecal GISTs from six mice. Note the unilateral tumor growth in relation to the cecal lumen in both genotypes and the compressed luminal diameter in KitV558Δ/+ mice. (C) Tumor weights. n = 3–6. Error bars indicate mean ± SD. (D) Kaplan–Meier survival plot showing reduced survival of KitV558Δ;Y567F/+ and KitV558Δ;Y567F/V558Δ;Y567F mice compared with KitV558Δ;Y567F/Y567F mice. The median survival of KitV558Δ;Y567F/+ and KitV558Δ;Y567F/V558Δ;Y567F mice was 15 (n = 16) and 7 (n = 46) months, respectively, and the median survival of KitV558Δ;Y567F/Y567F was 21 mo (n = 121), as shown in Fig. 1. (E) Comparison of KIT expression and downstream signal transduction in GISTs of 3- to 4-mo-old mice by immunohistochemistry. (Scale bars: 500 µm in a–c, 200 µm in d–i, and 50 µm in j–l.) (F and G) Immunoblot analysis (G) and its quantification (F). n.s., nonsignificant. Scale is in arbitrary units (intensity of gray shading).