Extended Data Fig. 1: CRISPR-Cas9 modified EGFR mutant PC-9 cells for evaluating oncogenicity of KRAS or BRAF mutations.
From: Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers
a, A schema of selection with EGFR inhibitor osimertinib. Majority of parental EGFR-mutant PC-9 cells are sensitive to osimertinib with only a small fraction exhibiting intrinsic resistance. In bulk CRISPR-Cas9 modified PC-9 cells, osimertinib treatment can lead to an increase in the fraction of cells harboring a resistance mutation such as KRAS G12C. b, Cell viability assay of parental and CRISPR-Cas9 modified PC-9 cells after 72 h of osimertinib treatment. Each clone has heterozygous KRAS mutations: GQ60GK c.180_181delinsCA plus Q61K, GQ60GK c.180_181delinsGA plus frameshift, and Q61K plus frameshift (n = 3 biological replicates, mean ± s.d.). c, Knockdown of KRAS or BRAF in CRISPR-Cas9-modified PC-9 clones following 48 h of KRAS or BRAF specific siRNA treatment are shown by western blot analyses.
