Extended Data Fig. 7: Drug sensitivity assay of NRASQ61K mutant organoids.
(a) qRT-PCR analysis of ETV4, ETV5, DUSP4, DUSP5 and CCND1 mRNA levels. These transcripts were compared between NRAS wildtype parental clone (WT) and NRAS-Q61K clone cultured in the medium with or without afatinib (Afa+/-). n = 2 clonal organoid lines. (b) Dose-response curves showing the sensitivity of NRAS-WT and NRAS-Q61K clones to inhibitors of the EGFR (Gefitinib), MEK (Trametinib), mTOR/PI3Kα (Everolimus/Alpelisib) and CDKs (Dinaciclib). Y-axis represent the viability of the samples while X-axis represent the drug concentration (power of 10 µM). Mean and SD (error bars) of n = 3 technical replicates for n = 2 independent organoid clones for each genetic background. (c) Representative bar graphs showing the sensitivity of NRAS-WT and NRAS-Q61K organoids to different inhibitors, calculated as area under the curve (AUC). n = 2 clonal organoid lines. (d) Heatmaps reporting the viability of the drug screening performed on NRAS-WT and NRAS-Q61K organoids as normalized to vehicle treated organoids. Color mapping range from low viability (red) to high viability (green).
