癌症是全球第二大死亡原因，预计未来几十年全球疾病负担将增加，其中大多数与癌症相关的死亡发生在转移性疾病中。癌症表现出已知的特征，赋予它们更高的存活率和增殖能力，这通常是不稳定突变的结果。然而，解析原发性肿瘤转移性克隆的基因组特征尚未得到充分表征，因为尚未确定突变景观可预测转移。此外，许多癌症没有表现出已知的突变特征。这表明非突变基因组重组在促进癌症进化和传播方面发挥着更大的作用。在这篇综述中，我们强调当前对了解转移性癌细胞的细胞状态转变和克隆选择优势的关键需求。我们研究了表观遗传状态、基因组结构以及肿瘤抑制因子和癌基因的失调之间的联系，并讨论了如何利用最新的技术来理解域尺度调控，以更全面地了解致癌和转移潜力。© 2024。作者）。

Cancer is the second leading cause of death worldwide and disease burden is expected to increase globally throughout the next several decades, with the majority of cancer-related deaths occurring in metastatic disease. Cancers exhibit known hallmarks that endow them with increased survival and proliferative capacities, frequently as a result of de-stabilizing mutations. However, the genomic features that resolve metastatic clones from primary tumors are not yet well-characterized, as no mutational landscape has been identified as predictive of metastasis. Further, many cancers exhibit no known mutation signature. This suggests a larger role for non-mutational genome re-organization in promoting cancer evolution and dissemination. In this review, we highlight current critical needs for understanding cell state transitions and clonal selection advantages for metastatic cancer cells. We examine links between epigenetic states, genome structure, and misregulation of tumor suppressors and oncogenes, and discuss how recent technologies for understanding domain-scale regulation have been leveraged for a more complete picture of oncogenic and metastatic potential.© 2024. The Author(s).