Division of Epigenomics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Science. 2021 Sep 24;373(6562):1474-1479. doi: 10.1126/science.abh1645. Epub 2021 Sep 23.
Cancer is a major cause of global mortality underpinned by genomic and epigenomic derangements. Here, we highlight the importance of multimodal data integration in understanding the molecular evolution of malignant cell states across the cancer life cycle. The widespread presence of driver mutations and epigenetic alterations in normal-appearing tissues is prompting a reassessment of how cancer initiation is defined. In later-stage cancers, studying the roles of clonal selection, epigenomic adaptation, and persister cells in metastasis and therapy resistance is an emerging field. Finally, the importance of tumor ecosystems in driving cancer development is being unraveled by single-cell and spatial technologies at unprecedented resolution. Improving cancer risk assessment and accelerating therapeutic discovery for patients will require robust, comprehensive, and integrated temporal, spatial, and multilevel tumor atlases across the cancer life cycle.
癌症是全球死亡率的主要原因，其基础是基因组和表观基因组的紊乱。在这里，我们强调了多模态数据集成在理解恶性细胞状态在整个癌症生命周期中的分子进化中的重要性。在外观正常的组织中广泛存在驱动突变和表观遗传改变，这促使人们重新评估如何定义癌症的发生。在晚期癌症中，研究克隆选择、表观遗传适应和持久性细胞在转移和治疗耐药性中的作用是一个新兴领域。最后，单细胞和空间技术以前所未有的分辨率揭示了肿瘤生态系统在推动癌症发展中的重要性。提高癌症风险评估和为患者加速治疗发现将需要在整个癌症生命周期中具有强大、全面和综合的时间、空间和多层次的肿瘤图谱。
