The initiation and progression of cancers reflect the underlying process of somatic evolution, in which the diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack access to (para)sexual recombination—a key diversification mechanism throughout all strata of life. On the basis of observations of spontaneous fusions involving cancer cells, the reported genetic instability of polypoid cells and the precedence of fusion-mediated parasexual recombination in fungi, we asked whether cell fusions between genetically distinct cancer cells could produce parasexual recombination. Using differentially labelled tumour cells, we found evidence of low-frequency, spontaneous cell fusions between carcinoma cells in multiple cell line models of breast cancer both in vitro and in vivo. While some hybrids remained polyploid, many displayed partial ploidy reduction, generating diverse progeny with heterogeneous inheritance of parental alleles, indicative of partial recombination. Hybrid cells also displayed elevated levels of phenotypic plasticity, which may further amplify the impact of cell fusions on the diversification of phenotypic traits. Using mathematical modelling, we demonstrated that the observed rates of spontaneous somatic cell fusions may enable populations of tumour cells to amplify clonal heterogeneity, thus facilitating the exploration of larger areas of the adaptive landscape (relative to strictly asexual populations), which may substantially accelerate a tumour’s ability to adapt to new selective pressures.

癌症的发生和发展反映了体细胞进化的基本过程，其中可遗传表型的多样化为自然选择提供了底物，导致最适合的亚群的生长。尽管体细胞进化可以利用多种多样化来源，但人们认为它缺乏（对）性重组的途径——这是一种贯穿所有生命阶层的关键多样化机制。基于对涉及癌细胞的自发融合的观察、报告的息肉细胞遗传不稳定性以及真菌中融合介导的副性重组的优先级，我们询问遗传不同的癌细胞之间的细胞融合是否可以产生副性重组。使用差异标记的肿瘤细胞，我们发现了低频的证据，在体外和体内的多种乳腺癌细胞系模型中，癌细胞之间的自发细胞融合。虽然一些杂种仍然是多倍体，但许多杂种表现出部分倍性减少，产生具有亲本等位基因异质遗传的多样化后代，表明部分重组。杂交细胞也表现出更高水平的表型可塑性，这可能会进一步放大细胞融合对表型性状多样化的影响。使用数学模型，我们证明了观察到的自发体细胞融合率可能使肿瘤细胞群能够放大克隆异质性，从而促进对更大范围的适应性景观（相对于严格的无性群体）的探索，