Fig. 5.

Potential molecular mechanisms of polyploid tumor formation. Distinct molecular alterations can influence each step of the progression from diploid to polyploid to tumorous proliferation. Shown here are recently identified mechanisms implicated in this progression. Genetic factors such as Rb loss or KLHDC88 mutation can promote endoreplication. Once cells achieve polyploidy, p53 can mediate cell cycle arrest or cell death. Conversely, in the absence of p53 or its target p21, or following administration of toxins such as diethylnitrosamine or aflatoxin B1 (see Reed et al., 2009 and McClendon et al., 2011), or in the presence of increased Myc (see Saddic et al., 2011), tumorigenesis may result.