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. 2022 Feb 1;13:604. doi: 10.1038/s41467-022-28198-8

Fig. 3. PPM1D is a dependency in PPM1Dtr but not PPM1D-WT cell lines.

Fig. 3

A Fold change in proliferation compared to day 0 of PPM1D-mutant patient-derived cell line (PDCL) BT869 after transfection with PPM1D-KO sgRNAs, nontargeting (LacZ) sgRNA, or lethal (EXOSC8) sgRNA. Growth curves show mean ± SEM from three replicates and are representative of three independent experiments. P = 0.0021, 0.0011, and 0.0016 for PPM1D-KO #1, PPM1D-KO #2, and EXOSC8 respectively calculated using two-tailed t-test. B Growth of PPM1D-WT PDCL SU-DIPG-IV after transfection with indicated sgRNAs. Growth curves show mean ± SEM from three replicates and are representative of three independent experiments. P = 0.8963, 0.5524, and 0.0335 for PPM1D-KO #1, PPM1D-KO #2, and EXOSC8 respectively calculated using two-tailed t-test. C Probability of PPM1D dependency as determined by pooled CRISPR-cas9 assays across 558 cancer cell lines, subgrouped according to their TP53 mutation and PPM1D copy-number status. Bounds of the box represent the IQR, center represents the median, and the bounds of the whiskers represent 1.5 times IQR. P < 0.0001 for TP53 WT/PPM1D non-amplified cells vs both TP53-mutant/PPM1D-amplified and TP53-mutant/PPM1D non-amplified cells and P < 0.01 for TP53 WT/PPM1D non-amplified cells vs TP53 WT/PPM1D-amplified cells using Kruskal–Wallis test. D Growth of PPM1D-mutant colon cell line HCT116 after transfection with indicated sgRNAs. Growth curves show mean ± SEM from three replicates and are representative of three independent experiments. P = 0.0015, 0.0010, and 0.0059 for PPM1D-KO #1, PPM1D-KO #2, and EXOSC8 respectively calculated using two-tailed t-test. E–F Growth of PPM1D-mutant DMG cell lines BT869 (E) and SF7761 (F) after treatment with vehicle control (NT), 10 μM of GSK2830371 (PPM1Di), 2 Gy of ionizing radiation treatment (RT), or the combination of both (GSK + RT). Growth curves show mean ± SEM from at least three replicates and are representative of three independent experiments. BT869: P = 4.90083E-06, 2.18655E−07, 3.83657E−11, 2.8877E−11, and 1.1625E−06 for NT vs PPM1Di, NT vs RT, NT vs PPM1Di + RT, RT vs PPM1Di + RT, and PPM1Di vs PPM1D + RT respectively calculated using two-tailed t-test; SF7761: P = 0.003367278, 1.17616E−05, 5.59401E−08, 1.5694E−08, and 2.698E−05 for NT vs PPM1Di, NT vs RT, NT vs PPM1Di + RT, RT vs PPM1Di + RT, and PPM1Di vs PPM1D + RT respectively calculated using two-tailed t-test. Source data are provided as a Source Data file.