Development and growth of all organisms involves the faithful reproduction
of cells and requires that the genome be accurately replicated and equally
partitioned between two cellular progeny. In human cells, faithful segregat
ion of the genome is accomplished by an elaborate macromolecular machine, t
he mitotic spindle. It is not difficult to envision how defects in componen
ts of this complex machine-molecules that control ifs organization and func
tion and regulators that temporally couple spindle operation to other cell
cycle events-could lead to chromosome missegregation. Recent evidence indic
ates that the persistent missegregation of chromosomes result in gains and
losses of chromosomes and may be an important cause of aneuploidy. This for
m of chromosome instability may contribute to tumor development and progres
sion by facilitating loss of heterozygocity (LOH) and the phenotypic expres
sion of mutated tumor suppressor genes, and by favoring polysomy of chromos
omes that harbor oncogenes. In this review, we will discuss mitotic defects
that cause chromosome missegregation, examine components and regulatory me
chanisms of the mitotic machine implicated in cancer, and explore mechanism
s by which chromosome missegregation could bad to cancer.