A novel source of tetraploid cancer cell precursors: telomere insufficiency links aging to oncogenesis.
Epithelial cancers of the elderly are caused by a combination of telomere dysfunction and the mutational invalidation of major tumor suppressors including p53. A recent article published in Cell by Davoli et al. shows that the simultaneous elimination of p53 and telomerase causes a state of chronic DNA damage that results in tetraploidization through endoreplication, that is, two consecutive S phases that are not separated by mitosis. As tetraploid cells represent a metastable intermediate between normal diploidy and cancer-associated aneuploidy, this novel route to tetraploidization may constitute (one of) the functional link(s) between aging and carcinogenesis.
Castedo
M
M
Institut Gustave Roussy, Villejuif, France. castedo@igr.fr
Vitale
I
I
Kroemer
G
G
D000368:Aged; D000375:Aging / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D004249:DNA Damage; D006801:Humans; D011123:Polyploidy; D016196:S Phase; D016615:Telomere