In any case, according to the branching evolutionary path of EGFRM+ LAC transforming to SCLC described by Lee et al. [200], the TKI-resistant SCLC clones emerged earlier and at much higher frequency from a founder LAC with complete (homozygous) inactivation of the tumor suppressor genes RB1 and TP53 at baseline as compared to LACs with intact p53 and Rb1 function. The gene discussed is TP53; the disease is small cell lung carcinoma.