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Does Cancer Solve an Optimization Problem?
Natalia Komarova
volume 3 | issue 7
july 2004Pages: 840 - 844
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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 sel¯sh 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* ~ ¼ 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 su±cient explanation for the presence of CIN in the majority of cancers.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.