Does cancer solve an optimization problem?

Many cancers are characterized by a high degree of aneuploidy, which is believed to be a result of chromosomal instability (CIN). The precise role of CIN in cancer is still the matter of a heated debate. We present a quantitative framework for examining the selection pressures acting on populations of cells and weigh the "pluses" and "minuses" of CIN from the point of view of a selfish cell. We calculate the optimal rate of chromosome loss assuming that cancer is initiated by inactivation of a tumor suppressor gene followed by a clonal expansion. The resulting rate, p(*)approximate to10(-2) per cell division per chromosome, is similar to that obtained experimentally by Lengauer et al. (1997). Our analysis further suggests that CIN does not arise simply because it allows a faster accumulation of carcinogenic mutations. Instead, CIN must arise because of alternative reasons, such as environmental factors, epigenetic events, or as a direct consequence of a tumor suppressor gene inactivation. The increased variability alone is not a sufficient explanation for the presence of CIN in the majority of cancers.