Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells

TLDR

Aneuploidy, an abnormal chromosome number, is a major cause of miscarriages, mental retardation, and a hallmark of cancer. The study generated primary mouse cell lines trisomic for one of four chromosomes to assess aneuploidy’s effects. All trisomic lines showed reduced proliferation, altered metabolism, and impaired immortalization, indicating that aneuploidy lowers cellular fitness and induces common traits across different aneuploid cells.

Abstract

Aneuploidy, an incorrect number of chromosomes, is the leading cause of miscarriages and mental retardation in humans and is a hallmark of cancer. We examined the effects of aneuploidy on primary mouse cells by generating a series of cell lines that carry an extra copy of one of four mouse chromosomes. In all four trisomic lines, proliferation was impaired and metabolic properties were altered. Immortalization, the acquisition of the ability to proliferate indefinitely, was also affected by the presence of an additional copy of certain chromosomes. Our data indicate that aneuploidy decreases not only organismal but also cellular fitness and elicits traits that are shared between different aneuploid cells.