PerspectiveCANCER

Preprocancer

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Science  22 May 2015:
Vol. 348, Issue 6237, pp. 867-868
DOI: 10.1126/science.aac4435

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Summary

Tumors have a life history (1, 2). A tumor consists of a dominant cell clone containing mutations in key cancer genes called “drivers,” together with smaller clones that descended from it but then diverged by accumulating different drivers. Other mutant clones appeared and vanished according to the selection pressures acting upon them or by neutral drift; the resulting diversity confers the means to escape clinical treatment (3). The stepwise accumulation of genetic and epigenetic alterations roughly parallels the clinical progression from normal tissue to precancer, cancer, and metastasis. It is widely assumed that driver mutations occur infrequently in long-lived lineages of cells (2), and that most arise in cancerous tissue that is too small to be clinically detectable. On page 880 of this issue, Martincorena et al. (4) overthrow both assumptions and reveal that sun-exposed normal skin is already a polyclonal quilt of driver mutations subjected to selection—a field of preprocancers, as it were—that nevertheless functions as a skin.