美国马萨诸塞州总医院和哈佛医学院Kamila Naxerova以及斯坦福大学医学院Johannes G. Reiter研究组合作取得一项新成果。经过不懈努力，他们发现与远处转移相比，淋巴结转移会形成更广泛的进化瓶颈。相关论文于2020年5月25日发表在《自然-遗传学》杂志上。

研究人员探究了临床预后不同的两处转移灶的病灶内和病灶间异质性，这两处转移灶分别为人结直肠癌的淋巴结转移灶和远处器官转移灶。研究人员利用严密的数学模型来量化转移灶系统发育的多样性。远处转移通常是单一来源的，并且在遗传上彼此相似。相反，淋巴结转移显示出高度的病灶间多样性。通过对来自20名患者的317个多区域活检分析，研究人员证实了这一特点。

进一步证明，与远处转移相比，淋巴结病变内异质性水平更高。该结果表明，远处转移的原发肿瘤谱系比淋巴结转移少，这表明两个部位的选择水平不同。因此，淋巴结和远处转移是通过根本不同的进化机制形成的。

据了解，关于转移之间的遗传多样性人类知之甚少，但转移含有关于继发部位疾病演变的重要信息。

附：英文原文

Title: Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases

Author: Johannes G. Reiter, Wei-Ting Hung, I-Hsiu Lee, Shriya Nagpal, Peter Giunta, Sebastian Degner, Gang Liu, Emma C. E. Wassenaar, William R. Jeck, Martin S. Taylor, Alexander A. Farahani, Hetal D. Marble, Simon Knott, Onno Kranenburg, Jochen K. Lennerz, Kamila Naxerova

Issue&Volume: 2020-05-25

Abstract: Genetic diversity among metastases is poorly understood but contains important information about disease evolution at secondary sites. Here we investigate inter- and intra-lesion heterogeneity for two types of metastases that associate with different clinical outcomes: lymph node and distant organ metastases in human colorectal cancer. We develop a rigorous mathematical framework for quantifying metastatic phylogenetic diversity. Distant metastases are typically monophyletic and genetically similar to each other. Lymph node metastases, in contrast, display high levels of inter-lesion diversity. We validate these findings by analyzing 317 multi-region biopsies from an independent cohort of 20 patients. We further demonstrate higher levels of intra-lesion heterogeneity in lymph node than in distant metastases. Our results show that fewer primary tumor lineages seed distant metastases than lymph node metastases, indicating that the two sites are subject to different levels of selection. Thus, lymph node and distant metastases develop through fundamentally different evolutionary mechanisms.

DOI: 10.1038/s41588-020-0633-2

Source: https://www.nature.com/articles/s41588-020-0633-2