Comprehensive characterization of transcriptomic changes in a large panel of H3122 EML4-ALK+ NSCLC cells spontaneously acquring resistance to ALK inhibition. ALKi-resitant H3122 cells

In this study we used the ALK inhibitor sensitive EML4-ALK translocation positive non-small cell lung cancer (NSCLC) cell line NCI-H3122 and isolated 24 cell clones (H3122res) independently acquiring resistance to ALK inhibition. We then characterized the transcriptomes by 3'mRNA-seq in comparison to biological replicate cultures (n=3) of parental H3122 cells. We find diversity but also common transcriptome changes in ALK inhibitor resistant H3122res cells including EMT-like phenotype changes. Further analyses and functional characterization identified the ID-family (inhibitor of differentiation) of transcriptinal regulators as important regulatory hub for restoring and sustaining cell cycle progression of drug-tolerant cells.