Cancer research has traditionally focused on the characterization of individual molecular mechanisms that can contribute to cancer. Due to the multiple levels of genomic and non-genomic heterogeneity, however, overwhelming molecular mechanisms have been identified, most with low clinical predictability. It is thus necessary to search for new concepts to unify these diverse mechanisms and develop better strategies to understand and treat cancer. In recent years, two-phased cancer evolution (comprised of the genome reorganization-mediated punctuated phase and gene mutation-mediated stepwise phase), initially described by tracing karyotype evolution, was confirmed by the Cancer Genome Project. In particular, genome chaos, the process of rapid and massive genome reorganization, has been commonly detected in various cancers—especially during key phase transitions, including cellular transformation, metastasis, and drug resistance—suggesting the importance of genome-level changes in cancer evolution. In this Perspective, genome chaos is used as a discussion point to illustrate new genome-mediated somatic evolutionary frameworks. By rephrasing cancer as a new system emergent from normal tissue, we present the multiple levels (or scales) of genomic and non-genomic information. Of these levels, evolutionary studies at the chromosomal level are determined to be of ultimate importance, since altered genomes change the karyotype coding and karyotype change is the key event for punctuated cellular macroevolution. Using this lens, we differentiate and analyze developmental processes and cancer evolution, as well as compare the informational relationship between genome chaos and its various subtypes in the context of macroevolution under crisis. Furthermore, the process of deterministic genome chaos is discussed to interpret apparently random events (including stressors, chromosomal variation subtypes, surviving cells with new karyotypes, and emergent stable cellular populations) as nonrandom patterns, which supports the new cancer evolutionary model that unifies genome and gene contributions during different phases of cancer evolution. Finally, the new perspective of using cancer as a model for organismal evolution is briefly addressed, emphasizing the Genome Theory as a new and necessary conceptual framework for future research and its practical implications, not only in cancer but evolutionary biology as a whole.

癌症研究传统上侧重于对可能导致癌症的个体分子机制的表征。然而，由于基因组和非基因组异质性的多层次，已经确定了压倒性的分子机制，大多数具有低临床可预测性。因此，有必要寻找新的概念来统一这些不同的机制，并制定更好的策略来理解和治疗癌症。近年来，癌症基因组计划证实了最初通过追踪核型进化描述的两阶段癌症进化（包括基因组重组介导的间断阶段和基因突变介导的逐步阶段）。特别是基因组混乱，快速和大规模的基因组重组过程，已在各种癌症中普遍检测到——尤其是在关键阶段转变期间，包括细胞转化、转移和耐药性——这表明基因组水平变化在癌症进化中的重要性。在这个观点中，基因组混沌被用作一个讨论点来说明新的基因组介导的体细胞进化框架。通过将癌症重新表述为从正常组织中出现的新系统，我们展示了基因组和非基因组信息的多个层次（或尺度）。在这些水平中，染色体水平的进化研究被认为是最重要的，因为改变的基因组改变了核型编码，而核型变化是间断细胞宏观进化的关键事件。使用这个镜头，我们区分和分析发育过程和癌症进化，以及在危机下的宏观进化背景下比较基因组混沌与其各种亚型之间的信息关系。此外，讨论了确定性基因组混乱的过程，以将明显的随机事件（包括压力源、染色体变异亚型、具有新核型的存活细胞和出现的稳定细胞群）解释为非随机模式，这支持了新的癌症进化模型，该模型统一了基因组和癌症进化不同阶段的基因贡献。最后，简要阐述了使用癌症作为有机体进化模型的新观点，强调基因组理论是未来研究及其实际意义的新的和必要的概念框架，不仅在癌症中，而且在整个进化生物学中。