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* = 10(-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.
Komarova
Natalia
N
Department of Mathematics, Rutgers University, Piscataway, New Jersey 08854, USA. natalia@ias.edu
D000782:Aneuploidy; D002274:Carcinogens, Environmental / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D043171:Chromosomal Instability / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism
D002274:Carcinogens, Environmental