Heterogeneity and Tumor History

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Science  20 Apr 2012:
Vol. 336, Issue 6079, pp. 304-305
DOI: 10.1126/science.1222361

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All cells are almost perfect copies of prior cells. Imperfect DNA replication creates random variation, which is the substrate for evolution. Such differences may be small [normally about one new mutation per human cell division (1)], but the accumulation of mutations over time can eventually transform a single cell. Progeny of this first transformed cell expand by bifurcating branching cell division (see the figure) to form visible billion-cell clonal tumor populations. Each one of these cancer cells is an almost perfect copy of the first transformed cell. Given this scenario, different genetic alterations in different parts of the same cancer should be found in most tumors. Such intratumor heterogeneity has been found in many cancers, but its true extent is becoming much more evident with the unprecedented ability to sequence genome-wide many times (deep sequencing).