FIGURE 3.

NGS analyses before and after therapy. NGS analysis before crizotinib treatment revealed the presence of the ALK fusion (A) plus the F1174L-cis-S1189C mutation (B). NGS analysis after crizotinib and ceritinib treatment revealed the presence of the ALK fusion (C) plus the F1174L-cis-S1189C mutation (D). (E) ALK structure retrieved from PDB 2XP2. In silico mutagenesis of human ALK binding to three ALK inhibitor complexes (PDB ID: 2XP2, PDB ID: 4MKC, and PDB ID: 3AOX) was used to predict the variable influence on protein stability. The dStability and relative thermostability of the mutation with respect to the wild-type protein are shown in the table.