Cancer is traditionally labeled a “cellular growth problem.” However, it is fundamentally an issue of macroevolution where new systems emerge from tissue by breaking various constraints. To study this process, we used experimental platforms to “watch evolution in action” by comparing the profiles of karyotypes, transcriptomes, and cellular phenotypes longitudinally before, during, and after key phase transitions. This effort, alongside critical rethinking of current gene-based genomic and evolutionary theory, led to the development of the Genome Architecture Theory. Following a brief historical review, we present four case studies and their takeaways to describe the pattern of genome-based cancer evolution. Our discoveries include 1. The importance of non-clonal chromosome aberrations or NCCAs; 2. Two-phased cancer evolution, comprising a punctuated phase and a gradual phase, dominated by karyotype changes and gene mutation/epigenetic alterations, respectively; 3. How the karyotype codes system inheritance, which organizes gene interactions and provides the genomic basis for physiological regulatory networks; and 4. Stress-induced genome chaos, which creates genomic information by reorganizing chromosomes for macroevolution. Together, these case studies redefine the relationship between cellular macro- and microevolution: macroevolution does not equal microevolution + time. Furthermore, we incorporate genome chaos and gene mutation in a general model: genome reorganization creates new karyotype coding, then diverse cancer gene mutations can promote the dominance of tumor cell populations. Finally, we call for validation of the Genome Architecture Theory of cancer and organismal evolution, as well as the systematic study of genomic information flow in evolutionary processes.

癌症传统上被称为“细胞生长问题”。然而，从根本上说，这是一个宏观进化问题，即通过打破各种限制从组织中出现新系统。为了研究这个过程，我们使用实验平台通过纵向比较关键相变之前、之中和之后的核型、转录组和细胞表型的概况来“观察进化过程”。这一努力，连同对当前基于基因的基因组和进化理论的批判性反思，导致了基因组架构理论的发展。在简短的历史回顾之后，我们提出了四个案例研究及其要点来描述基于基因组的癌症进化模式。我们的发现包括 1. 非克隆染色体畸变或 NCCA 的重要性；2. 两阶段癌症进化，包括间断阶段和渐进阶段，分别以核型变化和基因突变/表观遗传改变为主；3. 核型如何编码系统遗传，组织基因相互作用并为生理调节网络提供基因组基础；和 4. 压力引起的基因组混乱，通过重组染色体进行宏观进化来创建基因组信息。总之，这些案例研究重新定义了细胞宏观和微观进化之间的关系：宏观进化不等于微观进化 + 时间。此外，我们将基因组混乱和基因突变纳入了一个通用模型：基因组重组创造了新的核型编码，然后多样化的癌症基因突变可以促进肿瘤细胞群的优势。最后，