Thesis Defense Mar Soto: Why cancer cells tolerate chromosome imbalances

Gains and losses of chromosomes

It has widely been shown that gains and losses of chromosomes have very detrimental consequences in healthy cells and very few chromosomal abnormalities are compatible with human life. However, the vast majority of tumors are aneuploid, which means that their cells harbour a wrong number of chromosome. In order to get some insight understanding such a paradox, the researchers focused on the immediate and long-term consequences of aneuploidy in normal cells. 

What influences tolerance to imbalances?

They developed a system to generate aneuploid cells and found three factors that influenced tolerance to aneuploidy:

1. The number of chromosomes gained or lost 
2. Chromosome losses were less well tolerated than chromosome gains
3. Imbalances of whole chromosomes could be tolerated whereas gains or losses of pieces of chromosomes were not.

Guardian of the genome

Interestingly, they also found that p53, the gene known as the guardian of the genome, has a pivotal role in such tolerance. Since it is already known that the majority of the tumors lack functional p53, the data described in this thesis helps to understand the difference in tolerance to so-called aneuploidy between healthy and tumors cells.

Read more on the Utrecht University website.