Figure 3.

Divergent (branching) clonal evolution of cancer with topographical separation.

In each example, a clonal (single cell) ancestry is indicated by shared acquired mutations, e.g. ETV6-RUNX1 fusion for the leukaemias, c-kit mutation for the testicular cancers. The time at which the two subclones evolve (T₁, T₂) can be temporarily synchronous or develop several years apart^37,55–57. The probabilities of sub-clones emerging as shown are independent and different (p₁, p₂). In most cases (90% for monozygotic twins), only one twin develops overt leukaemia. The penetrance of bilateral testicular cancer having a common origin⁵⁷ is unknown.