Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Trends Genet. 2023 Dec;39(12):954-967. doi: 10.1016/j.tig.2023.08.004. Epub 2023 Sep 14.
The overwhelming majority of proliferating somatic human cells are diploid, and this genomic state is typically maintained across successive cell divisions. However, failures in cell division can induce a whole-genome doubling (WGD) event, in which diploid cells transition to a tetraploid state. While some WGDs are developmentally programmed to produce nonproliferative tetraploid cells with specific cellular functions, unscheduled WGDs can be catastrophic: erroneously arising tetraploid cells are ill-equipped to cope with their doubled cellular and chromosomal content and quickly become genomically unstable and tumorigenic. Deciphering the genetics that underlie the genesis, physiology, and evolution of whole-genome doubled (WGD) cells may therefore reveal therapeutic avenues to selectively eliminate pathological WGD cells.
绝大多数增殖的体细胞核型为二倍体，这种基因组状态通常在连续的细胞分裂中得以维持。然而，细胞分裂的失败会导致全基因组加倍（WGD）事件，使二倍体细胞转变为四倍体状态。虽然有些 WGD 是为了产生具有特定细胞功能的非增殖性四倍体细胞而进行的发育编程，但非计划的 WGD 可能是灾难性的：错误出现的四倍体细胞无法应对其两倍的细胞和染色体含量，很快就会变得基因组不稳定并癌变。因此，阐明全基因组加倍（WGD）细胞的发生、生理和进化的遗传学基础，可能会揭示出选择性消除病理性 WGD 细胞的治疗途径。
