Missegregation Causes Potential Cancers Millions of Times every Day

People ask: Why do we get cancer? But perhaps it would be more pertinent to ask: Why do we not get cancer? Cells mis-segregate in about 1 percent of divisions, which means that you have a beginning of aneuploidy or potential cancer millions of times every day. If a trisomic cell (a typical result of missegregation) is allowed to divide the progeny becomes susceptible to the highly mutagenic effects of breakage-fusion-bridge cycles or to chromothripsis, where the surplus chromosome is shattered and the pieces inserted at random in the corresponding chromosome, but also elsewhere in the genome. The organism has a number of mitigating mechanisms to prevent that run-away mis-segregation/chromosome instability turns into cancer. The first line of prevention is a roll-back of the mis-segregation itself, and the cell becomes tetraploid. A second line of prevention is cell division arrest. A third line of prevention is the cellular suicide: apoptosis. A further prevention mechanism is elimination by the immune system. If all prevention mechanisms are circumvented in a cell line the result could be cancer. Large, long lived animals rarely get cancer (Peto’s paradox); they seem to have many more genes for prevention mechanisms.