We asked whether single circulating tumor cell (CTC) sequencing can inform on resistance mutations to ALK inhibitors and underlying tumor heterogeneity in ALK-rearranged NSCLC....We investigated the VAF of resistance mutations in CTCs from 14 ALK-rearranged patients progressing on crizotinib...P13 harbored an ALKL1196M mutation in the tumor biopsy that was not detected in CTCs, whereas a total of 19 “off-target” mutations including eight TP53 mutations were detected in the 14 CTC specimens of this patient...