美国斯坦福大学Christina Curtis研究组利用匹配原发肿瘤和转移瘤，对多种肿瘤的克隆性和全身转移时机进行了综合分析。相关论文于2020年5月18日在线发表于《自然—遗传学》。
研究人员分析了来自136例乳腺癌、结直肠癌和肺癌患者的457对匹配的原发性肿瘤和转移性样本的全基因组测序（WES）数据，包括未治疗（n=99）和治疗（n=100）转移灶。经过治疗的转移瘤通常带有隐蔽的“驱动”突变，而未经治疗的转移瘤则没有，这表明治疗可以促进克隆的进化。
在未经治疗的淋巴结转移中（n=17，占29例中的59％）以及远端转移（n=20，占70例中的29％），多克隆转移很常见，但是在经过治疗的远端转移中（n=9，占94例的10％）则频率更低。低数量的隐蔽型转移克隆突变与早期转移一致，研究人员估计这些转移发生在诊断出这些癌症之前的2-4年。
此外，这些数据表明，相对于早期肿瘤发生，转移的自然过程是相对无规律的，而隐蔽型转移突变不是癌症扩散的驱动原因，但与耐药性有关。
据了解，转移是与癌症相关死亡的主要原因，但是人们对发生史、克隆进化和治疗效果了解甚少。
附：英文原文
Title: Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases
Author: Zheng Hu, Zan Li, Zhicheng Ma, Christina Curtis
Issue&Volume: 2020-05-18
Abstract: Metastasis is the primary cause of cancer-related deaths, but the natural history, clonal evolution and impact of treatment are poorly understood. We analyzed whole-exome sequencing (WES) data from 457 paired primary tumor and metastatic samples from 136 patients with breast, colorectal and lung cancer, including untreated (n=99) and treated (n=100) metastases. Treated metastases often harbored private ‘driver’ mutations, whereas untreated metastases did not, suggesting that treatment promotes clonal evolution. Polyclonal seeding was common in untreated lymph node metastases (n=17 out of 29, 59%) and distant metastases (n=20 out of 70, 29%), but less frequent in treated distant metastases (n=9 out of 94, 10%). The low number of metastasis-private clonal mutations is consistent with early metastatic seeding, which we estimated occurred 2–4 years before diagnosis across these cancers. Furthermore, these data suggest that the natural course of metastasis is selectively relaxed relative to early tumorigenesis and that metastasis-private mutations are not drivers of cancer spread but instead associated with drug resistance.
DOI: 10.1038/s41588-020-0628-z
Source: https://www.nature.com/articles/s41588-020-0628-z
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
