斯坦福大学医学院Christina Curtis研究组发现结肠癌会在早期发生系统性地扩散，并且提供了定量证据。相关研究内容发表在2019年7月出版的《自然—遗传学》杂志上。

研究组对23名有肝脏或脑部转移情况的结肠癌患者的118组视网膜组织切片的进行了外显子测序，接着对得到的数据进行分析，以此来描述了这种致命过程的进化动力学。数据显示,原发肿瘤和转移之间的基因差异较低,规范驱动基因很早就获得了。在空间内肿瘤生长模型和统计推断框架内地分析表明当这种癌症在临床上还检测不到的时候（（肿瘤体积）通常小于0.01cm³），早期散播转移已经很常见了(81%,21名评估的患者中有18人发生转移)。该课题组研究人员在一个有2751结肠癌样本的独立队列中，验证了早期驱动转移之间的关系，证明了它们作为肿瘤标志物的作用。这一概念和分析框架提供了体内定量证据，表明系统性扩散可在结直肠癌早期发生，并阐明了患者分层和肿瘤发生典型驱动因素治疗靶向的策略。

据悉，（结肠癌）转移时间和分子决定因素都是未知的，阻碍了治疗和预防工作。

附：英文原文

Title: Quantitative evidence for early metastatic seeding in colorectal cancer

Author: Zheng Hu, Jie Ding, Zhicheng Ma, Ruping Sun, Jose A. Seoane, J. Scott Shaffer, Carlos J. Suarez, Anna S. Berghoff, Chiara Cremolini, Alfredo Falcone, Fotios Loupakis, Peter Birner, Matthias Preusser, Heinz-Josef Lenz, Christina Curtis

Issue&Volume:  Volume 51 Issue 7, July 2019

Abstract: Both the timing and molecular determinants of metastasis are unknown, hindering treatment and prevention efforts. Here we characterize the evolutionary dynamics of this lethal process by analyzing exome-sequencing data from 118biopsies from 23patients with colorectal cancer with metastases to the liver or brain. The data show that the genomic divergence between the primary tumor and metastasis is low and that canonical driver genes were acquired early. Analysis within a spatial tumor growth model and statistical inference framework indicates that early disseminated cells commonly (81%, 17 out of 21evaluable patients) seed metastases while the carcinoma is clinically undetectable (typically, less than 0.01cm3). We validated the association between early drivers and metastasis in an independent cohort of 2,751colorectal cancers, demonstrating their utility as biomarkers of metastasis. This conceptual and analytical framework provides quantitative in vivo evidence that systemic spread can occur early in colorectal cancer and illuminates strategies for patient stratification and therapeutic targeting of the canonical drivers of tumorigenesis.

DOI: 10.1038/s41588-019-0423-x

Source: https://www.nature.com/articles/s41588-019-0423-x