Acquired resistance to entrectinib or crizotinib drives differential gene expression in ROS1+ NSCLC

Utilizing primary, patient tumor-derived ROS1+ NSCLC cell lines, we derived TKI-resistant cell lines by chronic exposure to TKI in the media. One of our parental, ROS1 TKI-sensitive cell lines harbors a TPM3-ROS1 fusion (CUTO28) and the other harbors a CD74-ROS1 fusion (CUTO37). Entrectinib-resistant (-ER) and crizotinib-resistant (-CR) lines are so named when they are stably proliferating at 500nM concentration of the respective TKI. We sought to investigate transcriptome changes with acquired resistance to entrectinib or crizotinib. Triplicate samples were submitted and analyzed per cell line for bulk RNA sequencing, with the exception of CUTO28-ER where one sample was found to be an outlier and thus duplicates were analyzed. One sample per cell line was submitted for whole exome sequencing.