Ticking Down to Metastasis

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Science  11 Apr 2008:
Vol. 320, Issue 5873, pp. 157
DOI: 10.1126/science.320.5873.157a

The idea that the accumulation of mutations is a type of clock that can be used to chart the developmental or evolutionary history of cells or organisms is well established. Adapting this mode of analysis, Jones et al. have catalogued mutations that occur during the stages of colorectal cancer, focusing on the poorly understood transition from advanced carcinoma to metastasis. They model the rates of appearance of mutations found in a large-scale survey of colorectal cancer (see Wood et al., Research Articles, 16 Nov. 2007, p. 1108). Mutation rates were determined by combining the numbers of mutations with estimates of cell division time, under the assumption that mutation rate and cell division time were constant in each patient. They conclude that it takes roughly 17 years for a large adenoma, which is benign, to evolve into an advanced carcinoma, which is malignant, but less than 2 years for that carcinoma to begin to metastasize. Evolution occurs through cycles of clonal expansion and mutation, and their model provides estimates of the “birth dates” of the founder cells. Although some metastasis-specific alterations were identified, the authors consider that all or most of the mutations needed for metastasis may already be present in the carcinomas. — BRJ

Proc. Natl. Acad. Sci. U.S.A. 105, 4283 (2008).

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