From polyploidy to aneuploidy, genome instability and cancer

Abstract

Polyploidy is a frequent phenomenon in the eukaryotic world, but the biological properties of polyploid cells are not well understood. During evolution, polyploidy is thought to be an important mechanism that contributes to speciation. Polyploid, usually non-dividing, cells are formed during development in otherwise diploid organisms. A growing amount of evidence indicates that polyploid cells also arise during a variety of pathological conditions. Genetic instability in these cells might provide a route to aneuploidy and thereby contribute to the development of cancer.

Ectopic Tbx2 expression results in polyploidy and cisplatin resistance

“…These results are in agreement with previous reports that checkpoint activation is often only transient, with some cells 'slipping' past the arrest and producing a tetraploid population due to defective cell division (Storchova and Pellman, 2004). We next investigated whether the CT-Tbx2 cells do indeed have double the number of chromosomes compared to that contained in CT-E cells.…”

“…Polyploid cells with CIN can arise from a wide variety of cell cycle defects including chromosome missegregation, defective mitotic spindle function and defective cytokinesis (reviewed by Storchova and Pellman, 2004). Therefore, to identify defects in CT-Tbx2 cells that could have triggered mitotic catastrophe and subsequent polyploidy, we examined anaphase and telophase chromosomes of CT-Tbx2 cells by immunofluorescence microscopy.…”

“…More specifically how Tbx2 causes the doubling of chromosomes, resulting in polyploidy, in already transformed lines may provide a clue to this mechanism. Polyploidy can be generated from a wide variety of errors in cell division (Nigg, 2002;Storchova and Pellman, 2004). For example, anaphase chromosome segregation and cytokinesis are tightly coordinated Ectopic expression of Tbx2 results in polyploidy E Davis et al processes that have to be completed with high fidelity and are therefore regulated by complex surveillance mechanisms.…”

“…When defects in either of these processes are detected a cell cycle arrest is imposed. In the event that these surveillance mechanisms are compromised cells can 'slip past' this arrest (Storchova and Pellman, 2004) resulting in polyploid cells. Initially, FACS analysis of CT-Tbx2 cells indicated that they were experiencing a cell cycle block in G 2 or M, which prevented cells from undergoing cytokinesis.…”

Interference of the dominant negative helix–loop–helix protein ID1 with the proteasomal subunit S5A causes centrosomal abnormalities

“…Cytokinesis failure or cell fusion gives rise to tetraploid cells that contain two centrosomes in G1. When such abnormal cells reenter the cell cycle, each centrosome is normally duplicated during S-phase resulting in a tetrapolar mitosis that may give rise to aneuploid progeny (reviewed in Storchova and Pellman, 2004). Certain oncogenic insults result in uncoupling of centrosome duplication from DNA replication and abnormal centrosome numbers arise in diploid cells (Duensing et al, 2001).…”