Fig. 1

Aneuploidy, CIN and GIN loop together to tumorigenesis. Aneuploidy results in direct changes in mRNA and protein expression levels of genes found on the aneuploid chromosome. Increasing or decreasing the dosage of oncogenes (OG) and tumor suppressor genes (TSG) can have direct effects on cellular transformation. Additionally, while CIN leads to aneuploidy via increased chromosome missegregation, aneuploidy can lead to CIN by changing the stoichiometry of protein complexes required for genome maintenance or by scaling defects brought about by the presence of extra DNA. At the same time, chromosome missegregation has the potential to increase DNA damage and GIN. CIN and GIN are considered mutator phenotypes that could potentially enhance the chance of accumulating oncogenic mutations, thus promoting tumorigenesis. Their ‘by-products’, aneuploidy and DNA damage generate genetic variation, allowing cells to have increased adaptive potential in the tumor microenvironment