LUMC researchers find cause of duplications in DNA that can lead to cancer

13 August 2021• NEWSITEM

Researchers at Leiden University Medical Centre (LUMC) discovered that the repair of DNA breaks is the cause of duplications of small pieces of DNA, which in turn can lead to cancer. Until now, it was unknown how these mutations arose. By inhibiting certain repair factors, the researchers saw fewer of these types of mutations. Since chemotherapy can also lead to duplications that can cause cancer in rare cases, the scientists want to investigate whether they can reduce this risk even further with their newly acquired knowledge. The results have been published in Nature Communications.

"Duplications of small pieces of DNA are common in our genome, but in some cases can have unpleasant consequences," says Joost Schimmel, researcher at the Department of Human Genetics. "For example, a quarter of patients with an aggressive form of blood cancer, or acute myeloid leukaemia, have a small duplication in the so-called FLT3 gene, which causes cells to grow uninhibited, and thus blood cancer." Other genes in which a duplication can lead to the development of cancer are also known. Exactly how these mutations arise was a mystery until now. "We have now discovered that the repair of DNA underlies this."

Deliberately damaging DNA 

The researchers saw that if they made a specific break in the DNA of cells in the laboratory, this was recognised by repair factors that fixed the break. Only, this often led to duplications. Schimmel: "We then inhibited one of these factors, a DNA polymerase, and saw far fewer duplications afterwards."

According to Marcel Tijsterman, Professor of Genome Stability, this is an important discovery because these duplications, such as in the FLT3 gene, can also occur during cancer treatment with radiation or chemotherapy. "This is because breaks in the DNA are made on purpose. Cancer cells in particular are sensitive to DNA damage and are eliminated in this way", says Tijsterman. If the duplications occur at a specific location in a specific gene, it can cause the development of new tumours in treated patients. But this is very rare. Tijsterman: "With this knowledge, we want to investigate in the future whether inhibiting some repair factors will make the risk of duplications after radiotherapy or chemotherapy, and therefore the risk of new tumours, even smaller." 

Read the entire article in Nature Communications.

Stay informed on the latest news of the Leiden University Medical Center, and sign up for our biweekly newsletter or subscribe to our LUMC Magazine.