遗传背景决定了实验性癌症进化的轨迹，这一成果由剑桥大学Duncan T. Odom小组经过不懈努力而取得。这一研究成果于2026年7月22日发表在国际顶尖学术期刊《自然》上。

据了解，人类癌症具有异质性。解剖生殖系遗传变异和环境因素如何影响人类进化主题数据集受到遗传背景和环境暴露的固有多样性的限制。为了克服这些限制，研究人员在不同的近交单主题菌株中重新运行了数百次早期肿瘤进化，产生了匹配的组织学和全基因组和转录组序列。性别、环境和致癌物暴露都是可控的，研究设计使他们能够捕捉到与在人类群体中观察到的遗传变异相比较的基因变异，同时利用菌株-垃圾-动物-肿瘤关系的嵌套层次结构。

研究分析表明，遗传背景和获得性体细胞突变之间的相互作用导致群体特异性疾病进展，包括驱动突变的选择、全基因组复制的发生和反映癌症易感性和肿瘤生长速度的亚克隆选择动力学。即使是适度的遗传差异，与人类祖先群体的差异相比，也能显著改变癌症发展过程中的选择压力，从而塑造癌症风险和肿瘤进化的轨迹。

附：英文原文

Title: Genetic background sets the trajectory of experimental cancer evolution

Author: Aitken, Sarah J., Connor, Frances, Feig, Christine, Rayner, Tim F., Lukk, Margus, Luft, Juliet, Aitken, Stuart, Arnedo-Pac, Claudia, Hayes, James F., Nicholson, Michael D., Ewing, Ailith, Sundaram, Vasavi, Verburg, Jan C., Connelly, John, Anderson, Craig J., Behm, Mikaela, Campbell, Susan, Daunesse, Malle, Kaiser, Vera B., Kentepozidou, Elissavet, Pich, Oriol, Redmond, Aisling M., Santoyo-Lopez, Javier, Sents, Ins, Talmane, Lana, Flicek, Paul, Lpez-Bigas, Nria, Semple, Colin A., Taylor, Martin S., Odom, Duncan T.

Issue&Volume: 2026-07-22

Abstract: Human cancers are heterogeneous1. Dissecting how germline genetic variation and environmental factors shape tumour evolution using human datasets is limited by inherent diversity in genetic backgrounds2 and environmental exposures3,4,5. Here, to overcome these limitations, we re-ran early tumour evolution hundreds of times in diverged inbred mouse strains, generating matched histology and whole-genome and transcriptome sequences. The sex, environment and carcinogenic exposures were all controlled, and the study design allowed us to capture genetic variation comparable with that observed across human populations while exploiting the nested hierarchical structure of strain–litter–animal–tumour relationships. Our analyses reveal that epistatic interactions between genetic background and acquired somatic mutations result in population-specific disease progression, including choice of driver mutations, occurrence of whole-genome duplication and subclonal selection dynamics that mirror both cancer susceptibility and tumour growth rate. Even modest genetic divergence, comparable with that found across human ancestry groups, can strikingly alter selection pressures during cancer development to shape both cancer risk and the trajectory of tumour evolution.

DOI: 10.1038/s41586-026-10821-z

Source: https://www.nature.com/articles/s41586-026-10821-z