INSERM U1037, Cancer Research Center in Toulouse (CRCT), 31037, Toulouse, France.
INSERM U1218, 229 cours de l'Argonne, 33076, Bordeaux, France.
Oncogene. 2019 Aug;38(33):6083-6094. doi: 10.1038/s41388-019-0859-6. Epub 2019 Jul 3.
Oncogenesis is considered to result from chromosomal instability, in addition to oncogene and tumor-suppressor alterations. Intermediate to aneuploidy and chromosomal instability, genome doubling is a frequent event in tumor development but the mechanisms driving tetraploidization and its impact remain unexplored. Cell fusion, one of the pathways to tetraploidy, is a physiological process involved in mesenchymal cell differentiation. Besides simple genome doubling, cell fusion results in the merging of two different genomes that can be destabilized upon proliferation. By testing whether cell fusion is involved in mesenchymal oncogenesis, we provide evidence that it induces genomic instability and mediates tumor initiation. After a latency period, the tumor emerges with the cells most suited for its development. Furthermore, hybrid tumor genomes were stabilized after this selection process and were very close to those of human pleomorphic mesenchymal tumors. Thus genome restructuring triggered by cell fusion may account for the chromosomal instability involved in oncogenesis.
肿瘤发生被认为除了癌基因和肿瘤抑制基因改变外，还源于染色体不稳定性。在非整倍体和染色体不稳定性之间，基因组加倍是肿瘤发生中的一个常见事件，但驱动四倍体形成的机制及其影响仍未被探索。细胞融合是四倍体形成的途径之一，是涉及间充质细胞分化的生理过程。除了简单的基因组加倍外，细胞融合还导致两个不同基因组的合并，在增殖过程中可能会不稳定。通过测试细胞融合是否参与间充质肿瘤发生，我们提供了证据表明它诱导了基因组不稳定性并介导了肿瘤起始。在潜伏期后，最适合其发展的细胞出现肿瘤。此外，在这个选择过程之后，杂交肿瘤基因组得到了稳定，并且非常接近人类多形性间充质肿瘤的基因组。因此，细胞融合引发的基因组重排可能解释了肿瘤发生中涉及的染色体不稳定性。
