Fig. 1: H2AX loss is frequently observed in BRCA-deficient mammary tumours with acquired PARPi resistance.
From: H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours
a Design of the genome-wide CRISPR-Cas9 genetic screen carried out in KB2P3.4 cells treated with the poly(ADP-ribose) polymerase (PARP) inhibitor AZD2461. b Venn diagram showing the overlap of potential gene candidates identified in each individual screen. c Violin plots showing the Z-Normalized Beta-Enrichment Score from 5 different genetic screens for chemoresistance carried out in different BRCA1/2-deficient cell lines. Data were all analyzed using the MAGeCK MLE algorithm to allow for cross comparison. d Design of an in vivo pipeline to query for genetic alterations and Homologous Recombination (HR) restoration in PARPi-resistant mammary tumours from KB1/2P mice. e Pie charts showing 45 and 34 PARPi-resistant mammary tumours from KB1P and KB2P mice, respectively. Tumours are grouped based on RAD51 IRIF+, Parg mutational status and H2afx gene expression (see Methods text).
