Figure 2.

Loss of BAP1 renders mesothelioma cells sensitive to mevalonate pathway inhibition

(A and B) Competitive growth assay showing a decrease in cell fitness upon expression of GFP-tagged gRNA targeting Pmvk (A) and Mvk (B) in BNC versus NC cells over 3 weeks. Data were normalized against day 8 after transfection (mean ± SD; n = 3 independent experiments). p values were determined by two-tailed unpaired Student’s t test; ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.

(C) Kaplan-Meier curve indicating overall survival (OS) of patients with mesothelioma based on expression of mevalonate pathway genes. Top quartile (25% of patients with highest expression) of mevalonate pathway gene expression versus bottom quartile (25% of patients with lowest expression). The graph depicts p value obtained using the log rank test.

(D) Kaplan-Meier curve indicating OS of patients (same cohort as in C) based on expression of MVK; log rank test.

(E and F) Colony-formation assays and quantifications showing sensitivity of BAP1-deficient mouse (E) and human (F) mesothelioma cells to zoledronic acid (μM) treatment compared with BAP1-proficient cell lines; representative data shown from three independent experiments. Quantification data are mean ± SEM, n = 3 independent experiments.

See also Figure S2.