In agreement with previous studies26, tumours with a combined histology at the time of first diagnosis (S02500, S02814 and S02917) also harboured TP53 and RB1 alterations as part of the common ancestor (Supplementary Appendix) whereas oncogenic mutations, such as in KRAS, were no longer apparent in relapsing tumours with SCLC histology19,27 (Fig. 4b). Here, RB1 is linked to small cell lung carcinoma.