Plain language summary: Coordinated inheritance of extrachromosomal DNAs in cancer cells
Below is a plain language summary of Coordinated inheritance of extrachromosomal DNAs in cancer cells, a paper published in Nature in November 2024 by Cancer Grand Challenges team eDyNAmiC.
It has been co-developed by the team eDyNAmiC patient advocates. It was written by Shirin Khalili, Katell Maguet, Dave Chuter, and Andrew Lang, based on first draft versions written by the first authors of the paper.
DNA breaks Mendelian rules of genetic inheritance when cancer cells divide
In normal cells, DNA is neatly organized into 23 pairs of chromosomes. However, in the cells of many different types of cancer, there are extra copies of certain genes that drive cancer growth. These extra gene copies can exist outside the chromosomes on circular pieces of DNA, which are called extrachromosomal DNA (ecDNA). When normal cells divide, their chromosomes are evenly distributed, resulting in identical daughter cells with two copies of each gene. But in cancer cells, ecDNAs are inherited unevenly in varying numbers, ranging from 5 to 200 copies.
These extra ecDNA copies may contain different cancer-driving genes that make the tumor grow faster and help it become resistant to cancer drugs. Studying how multiple copies of ecDNAs are distributed in cancer cells can help us understand how they keep specific combinations of genes as they grow and resist drug treatments. Team eDyNAmic previously showed that, surprisingly, ecDNA molecules can cooperate to enhance the expression of cancer-causing genes.
In this study, the Team used computational modelling to show that different ecDNAs containing cancer-promoting genes can be passed down together as a group when cancer cells divide. This surprising finding, which is not something that normal DNA can do, allows different ecDNAs to continue to work together in daughter cells to drive cancer growth. When these cells are exposed to a cancer drug, the numbers of unique ecDNAs decrease together, showing a coordinated response to treatment.
This study reveals that cancer cells can change their ecDNA content in a dynamic yet coordinated manner. It also shows how ecDNAs carrying different genes cooperate to turbo-charge cancer growth. These findings on ecDNA are significant because they add strong supporting evidence that science has been wrongly assuming that the same basic genetic rules apply to cancer cells as to healthy cells.
