Polyploidy in Liver Function, Mitochondrial Metabolism, and Cancer

The development of polyploid cells in tissues and organs is a highly regulated process. Polyploidy levels change profoundly during liver growth and maturation. Cytogenetic analyses of hepatocytes have shown that liver aneuploidy is widespread, with chromosome gains and losses occurring in an unbiased fashion. Experiments have shown that polyploidy is associated with specific gene expression patterns in yeast. Ploidy reversal might partially explain the capacity of the aged liver to regenerate, although regeneration is substantially reduced in elderly individuals. Liver regeneration and a host of liver diseases are associated with hepatic ploidy alterations and mitochondrial metabolic dysfunction. Many forms of cancer exhibit polyploidy at both early and late stages of disease, but in the context of hepatocellular carcinomas (HCC) a reduction of ploidy has been observed. HCC is the most common form of liver cancer and is associated with high mortality and morbidity worldwide.