Understanding aneuploidy tolerance in cancer by studying early embryogenesis

Project Information

OncoFetal_Ploidy

Grant agreement ID: 101068843

DOI

10.3030/101068843

Project closed

EC signature date 14 July 2022

Start date 1 July 2022

End date 30 November 2024

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 190 374,32

Coordinated by

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Netherlands

Periodic Reporting for period 1 - OncoFetal_Ploidy (Understanding aneuploidy tolerance in cancer by studying early embryogenesis)

Reporting period: 2022-07-01 to 2024-11-30

Summary of the context and overall objectives of the project

What is Aneuploidy?

Every human cell contains DNA that is packed into 46 chromosomes. Imagine these 46 chromosomes as instruction manuals in a library that help the cell operate its functions. Within the human body cells divide everyday. During cell divisions, errors can occur, and daughter cells can end up with extra or missing chromosomes - a condition called aneuploidy.

If chromosomes are like instruction manuals for the cells, missing a copy of a manual means losing crucial information, while an extra copy creates confusion about which version to use. Therefore, one might assume aneuploidy is always detrimental to the cell, however, it turns out it depends on a context.

What makes some cells tolerant to aneuploidy?

In the body cells can have different levels of specializations. “Specialized” cells perform specific tasks, for example red blood cells carry oxygen, muscle cells contract, nerve cells carry electrical impulses. “Unspecialized” cells haven’t been assigned a role yet—they can turn into different types of cells depending on what your body needs. Do those different types of cell specializations influence tolerance of aneuploidy? If yes, what are the mechanisms?

Why study aneuploidy?

Aneuploid cancer cells tend to be more resistant to the treatment, more prone to spread to other parts of the body, and aneuploid cancers tend to be associated with poorer prognosis for the patient. Understanding what allows cancer cells to tolerate a high degree of aneuploidy would allow us to understand the disease better, take actions to target those mechanisms, ultimately making the disease more manageable.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

How did the project move us closer to the answer?

Firstly, the project focused on building an experimental platform to study the question of how specialized and unspecialized cells deal with aneuploidy.

This means, choosing the best cells to study. Growing and genetically engineering cells so that they express colored proteins when they become specialized or unspecialized to help researchers distinguish between them. Optimising protocols to allow cells the optimal conditions to grow and divide happily under the microscope for several days, and to acquire high quality data at the same time.

Having gathered all of the information above the project was able to validate that the hypothesis was indeed correct – the cells deal differently with aneuploidy depending on how specialized they are. The unspecialized cells are more prone to making mistakes and tolerating them. The experiments are currently ongoing to understand why that is, and what sets unspecialized and specialized cells apart in that regard.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The study not only deepens scientific insight into the cellular aspects that influence aneuploidy occurrence and tolerance, it also paves the way for potential future advancements in cancer treatment.

Colon organoid with differently colored cells depending on their specialization