Fig. 2: H2AX depletion leads to PARPi resistance in vitro and in vivo.
From: H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours
a Clonogenic survival assay of KB2P3.4-derived cells treated, or mock treated, with the indicated concentrations of the PARPi olaparib and AZD2461 for 12 days. Plotted values express the mean ± SD of clonogenic survival (n = 3 independent experiments). P-values were calculated with two-way Anova test and adjusted for multiple comparisons. Source data are provided as a Source Data file. b Schematic design of the in vivo experiment. c Allelic modification rate of H2AX-deficient ORG-KB2P26N.1 organoids evaluated by TIDE analysis prior to transplantation. d Kaplan-Meier curves showing the survival of vehicle- or olaparib-treated mice bearing H2AX-proficient or deficient KB2P tumours. Each group contained 5 animals. P-value was calculated with the Mantel-Cox test. Source data are provided as a Source Data file. e Clonogenic survival assay of KB1P-G3-derived cells expressing the indicated H2AX variants and treated as in (a). Plotted values express the mean ± SD of clonogenic survival (n = 3 independent experiments). P-values were calculated with two-way Anova test and adjusted for multiple comparisons. Source data are provided as a Source Data file. f Therapy history of the CHIOVAR59 patient. On the right, H2AX IHC was performed on two tissue biopsies, primary tumour at diagnosis and colon metastasis after therapy resistance. Two areas of the slide are shown for each biopsy. Scale bar is 50 µm.
