Fig. 2: Mosaic somatic EGFR mutations mediate multiple primary lung tumors resulting from shared common ancestors.

WES-derived phylogenetic trees of four cases with multiple tumors that share a common somatic ancestor. The shared somatic mutations, including EGFR, are shown in magenta. Numbers on branches are mutations that accumulated between two nodes, which represent distinct clones identified by WES. Numbers in parentheses are exonic mutations that are not in the FFPE context. In comparison with the previous cases, the branches of these trees do intersect at the pink clones, indicating some shared genetic ancestry that is not observed in completely independent or germline tumors. However, the number of shared mutations and the trunk of shared ancestry are very small relative to the total number of mutations in each clone. This is distinct from the patients with metastatic cancer. The pie charts of these tumors all exhibit the pink clone but are otherwise relatively simple and do not share clones between tumors. a, In case 7, the two geographically distinct tumors share an extremely rare somatic EGFR mutation, SPKANTKEI752del, and then acquire 236 and 328 separate exonic mutations. b, In case 8, two geographically distinct contralateral tumors share the recurrent mutation L858R, in addition to two somatic mutations, before acquiring 111 and 83 separate mutations each. c, In case 9, two tumors (T2 and T6) share the L858R mutation before acquiring between 38 and 69 private mutations. T4 and T7 were too early stage and of too low purity to assess by WES whether they also carry the mutation; however, clinical sequencing confirmed the L858R mutation in both. d, In case 10, six tumors share XKR6 P580Q, ZBTB16 (intron) and ARID3B (3′-UTR) mutations. ^*EGFR L858R was found in three of the six tumors (T1, T6 and T7) by WES and a fourth (T4) by clinical genotyping. ^**ZBTB16 and AIRD3B mutations were observed in multiple tumors but not normal tissue samples, therefore they are borderline for FFPE filtering. The other two tumors are early stage and low purity. These tumors went on to acquire 45–409 private mutations.