Within the last two decades the advent of next generation sequencing accompanied by single-cell technologies has enabled cancer researchers to study in detail mutations and other genetic aberrations that transpire during transformation of cells to a neoplastic state. This article covers the insights gained through these extensive studies where neo-Darwinian principles can be inferred to play roles throughout neoplastic transformation. The cells promoted during cancer development exhibit cancer hallmarks combined with the related enabling characteristics as outlined by Hanahan and Weinberg, analogous to natural selection and survival of the fittest. Selection of driver mutations that inactivate proteins encoded by tumor suppressor genes differs in profound ways from mutations that activate tumor promoter proteins. In most cases the later stages of cancer development are characterized by sudden, extensive damage to chromosomes in a process that is not Darwinian in nature. Nevertheless, cells that survive these cataclysmic events remain subject to Darwinian selection promoting clones exhibiting the greatest rates of progression. Duplications of chromosomal segments containing oncogenes, deletions of segments harboring tumor suppressor genes, or distinctive chromosomal rearrangements are often found in cells progressing into later stages of cancer. In summary, the technological developments in genome sequencing since the start of the century have given us clear insights into genomic alterations promoting tumor progression where neo-Darwinian mechanisms of clonal selection can be inferred to play a primary role.

中文翻译：

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新达尔文主义原理在癌症基因组学中的体现

在过去的二十年里，伴随着单细胞技术的下一代测序的出现使癌症研究人员能够详细研究细胞转化为肿瘤状态期间发生的突变和其他遗传畸变。本文涵盖了通过这些广泛研究获得的见解，可以推断新达尔文原理在整个肿瘤转化过程中发挥着作用。癌症发展过程中促进的细胞表现出癌症标志以及哈纳汉和温伯格概述的相关促成特征，类似于自然选择和适者生存。使肿瘤抑制基因编码的蛋白质失活的驱动突变的选择与激活肿瘤启动子蛋白的突变有很大不同。在大多数情况下，癌症发展的后期阶段的特点是染色体突然受到广泛损伤，这一过程本质上不是达尔文式的。然而，在这些灾难性事件中幸存下来的细胞仍然受到达尔文选择的影响，促进克隆表现出最大的进展率。在进展到癌症后期的细胞中经常会发现含有癌基因的染色体片段的重复、含有肿瘤抑制基因的片段的缺失或独特的染色体重排。总之，自本世纪初以来基因组测序技术的发展使我们清楚地了解了促进肿瘤进展的基因组改变，其中可以推断新达尔文克隆选择机制发挥了主要作用。