Schematic illustration of the patterns of tumor recurrence. (A) In the ancestral cell origin model, therapeutic interventions removed all dominant disease clones from the primary tumor but not refractory ancestral cells. The ancestral cell accumulates new mutations and proliferates to become the recurrent tumor. In this model, mutations shared by primary and recurrent tumors were presumably only from the ancestral cell, and the two subsequent tumors were thus more divergent. (B) In the clonal evolution model, the treatment removed most of the primary tumor cells, but cells from the major primary disease clones survived and continued to grow to result in a recurrent tumor. During this process, additional mutations were accumulated and therefore detected in the recurrent tumor, and all primary tumor clonal mutations are retained in the recurrence.
