Cancer results from the acquisition of somatic alterations in a microevolutionary process that typically occurs over many years, much of which is occult. Understanding the evolutionary dynamics that are operative at different stages of progression in individual tumors might inform the earlier detection, diagnosis, and treatment of cancer. Although these processes cannot be directly observed, the resultant spatiotemporal patterns of genetic variation amongst tumor cells encode their evolutionary histories. Such intra-tumor heterogeneity is pervasive not only at the genomic level, but also at the transcriptomic, phenotypic, and cellular levels. Given the implications for precision medicine, the accurate quantification of heterogeneity within and between tumors has become a major focus of current research. In this review, we provide a population genetics perspective on the determinants of intra-tumor heterogeneity and approaches to quantify genetic diversity. We summarize evidence for different modes of evolution based on recent cancer genome sequencing studies and discuss emerging evolutionary strategies to therapeutically exploit tumor heterogeneity. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.

中文翻译：

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关于肿瘤内异质性决定因素的群体遗传学观点。

癌症是由微进化过程中获得的体细胞变化而引起的，这种变化通常发生多年，其中很多是隐匿的。了解在个体肿瘤的不同进展阶段可操作的进化动力学可能会为早期发现，诊断和治疗癌症提供信息。尽管不能直接观察到这些过程，但是肿瘤细胞间遗传变异的时空模式编码了它们的进化历史。这种肿瘤内异质性不仅在基因组水平上普遍存在，而且在转录组，表型和细胞水平上也普遍存在。考虑到对精密医学的影响，对肿瘤内和肿瘤间异质性的准确定量已成为当前研究的重点。在这篇评论中 我们为肿瘤内异质性的决定因素和量化遗传多样性的方法提供了群体遗传学的观点。我们基于最近的癌症基因组测序研究总结了不同进化模式的证据，并讨论了新兴的进化策略来治疗性利用肿瘤的异质性。本文是由Robert A. Gatenby博士编辑的题为：进化原理-癌症的异质性？的特刊的一部分。