Whole-genome doubling in tissues and tumors

Abstract

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.