Acquisition or emergence of preexisting clones with mutations in the MET activation loop Y1230 (also known as Y1248) or D1228 (also known as Y1246) has been shown to mediate resistance to type I MET TKI such as crizotinib in NSCLC with MET exon 14 skipping mutation. The gene discussed is MET; the disease is non-small cell lung carcinoma.