Study Reveals Even Transient Chromosomal Errors Can Initiate Cancer


We show that you don't need chronic, lifelong chromosomal mistakes to produce tumorigenesis at a quite respectable frequency, said Don Cleveland, Member of the Ludwig Institute for Cancer Research, San Diego, who led the study with Floris Foijer of the University of Groningen, in The Netherlands. A very transient exposure would likely be sufficient to drive a very substantial increase in tumorigenesis.

Boveri hypothesized that there would be specific combinations of gains and losses of chromosomes that could lead to cancer. We've now tested that and shown that not only was he right, but that even a short burst of chromosome instability is enough to induce these combinations, a postdoctoral researcher in Cleveland's lab and the study's first author.

In the study, Shoshani and his colleagues overexpressed the gene polo-like kinase 4 (Plk4) in mice. Plk4 is a master regulator that controls the number of centrosomes present inside a cell. Centrosomes play an important role in cell division by helping separate replicated chromosomes into two daughter cells. Normally, two centrosomes are present inside a cell during division, one at each pole of the cell.

However, when you overexpress Plk4, you have more than two, and this leads to chromosome missegregation, whereby the chromosomes are not being pulled correctly and the daughter cells inherit an unequal number of chromosomes.


Immunogenetics Open Access