Figure 3.

Types of multiple mutations (MM) within individual oncogenes. A, De novo MM. Two mutations (mutations A and B) within individual oncogenes are frequent (9% in primary untreated cancers) and are mostly located in cis. B, Secondary MM associated with drug‐resistant mutations. Tumors with hotspot mutations (mutation A) treated with molecularly targeted therapy often acquire secondary mutations (mutation B), which confer resistance to the therapy. C, MM from different subclones (left). Evolutionary trees illustrating MM causing parallel evolution (right). Two subclonal populations of tumor cells (subclones 1 and 2) independently acquire mutations (mutations A and B) in oncogene X, resulting in independent evolution