Attack of the clones

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Science  10 Oct 2014:
Vol. 346, Issue 6206, pp. 169-170
DOI: 10.1126/science.1259926

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Nearly 40 years ago, it was presciently observed (1) that each patient's cancer would require individual therapy and that this would be “thwarted” by the emergence of resistant cells. This prediction has proven to be depressingly true in various malignancies. It is now evident that malignant clones and subclones evolve not only through gradual acquisition of mutations but are also secondary to abrupt catastrophic events (such as massive chromosomal rerarrangement), leading to genomic heterogeneity in a tumor over time. The advent of next-generation sequencing has enabled these processes to be studied in unprecedented detail. Considerable intratumoral heterogeneity has been demonstrated in certain hematological malignancies and cancers of the breast, ovary, bladder, prostate, pancreas, and kidney (28). On pages 256 and 251 of this issue, Zhang et al. (9) and de Bruin et al. (10), respectively, describe the universal prevalence of intratumoral heterogeneity in lung cancer, with important implications for future research.