Figure 1. The lineage of mitotic cell divisions from the fertilized egg to a single cell within a cancer showing the timing of the somatic mutations acquired by the cancer cell and the processes that contribute to them.

Mutations may be acquired while the cell lineage is phenotypically normal, reflecting both the intrinsic mutations acquired during normal cell division and the effects of exogenous mutagens. During the development of the cancer other processes, for example DNA repair defects, may contribute to the mutational burden. Passenger mutations do not have any effect on the cancer cell, but driver mutations will cause a clonal expansion. Relapse after chemotherapy can be associated with resistance mutations that often predate the initiation of treatment.