PTEN and neoplasm: Of the remaining 28 patients who did not have an identified EGFR-based and/or MET-based osimertinib resistance mechanism, 18 had unknown mechanisms (of these, one had neither tissue nor ctDNA and 13 had ctDNA testing but no tumor testing), and 10 had EGFR-independent and/or MET-independent resistance mechanisms, such as alterations in PIK3CA, KRAS and PTEN, and mutations in cell cycle genes, identified by NGS (Fig. 2d and Supplementary Table 7).