Fig. 2

The proposed timeline that illustrates the relationship between various molecular mechanisms (summarized by the hallmarks of cancer, modified from reference [50, 139]), aneuploidy, CIN (often coupled with other karyotype alterations such as structural alterations and polyploidy), macro-evolution, micro-evolution and the clinically detectable tumor. As NCCAs can be detected from earlier developmental stages, the relationship between various molecular mechanisms and aneuploidy is less clear. It is clear, however, that there is a complex, interactive relationship. Furthermore, elevated CIN is important for triggering macro-cellular evolution, followed by micro-cellular evolution, leading ultimately to the proliferation of the cancer cells with the winning genome. This diagram highlights the complex, dynamic relationship between aneuploidy, CIN and the two phases (macro and micro) of cancer evolution