The strong presence of extrachromosomal circular DNA in some children could explain the mutations at the origin of cancers.
We are still struggling to determine where exactly cancers come from. Since they are associated with DNA defects that accumulate over time, scientists consider it to be an age-related disease. However, it raises the question: why do children get cancer?
A team of international researchers from the Charité hospital in Berlin (Germany) and the Memorial Sloan Kettering Cancer Center in New York (United States) may have found the beginning of an answer. Mysterious rings of DNA, known as extrachromosomal circular DNA, play a major role in the development of cancer in children. Scientists have drawn the first detailed map of circular DNA, which has given them a better understanding of the questions that the scientific community has long been asking about the genetics of cancer. Their work has been published in the journal Nature Genetics.
The youngest affected
Of the almost half a million people who develop cancer in Germany every year, around 2,100 are under the age of 18. Older people get cancer from lifestyle factors, such as tobacco smoke, or even from outside causes, such as radiation that damages cell DNA. If left unchecked for years, affected cells lose control of cell growth and division, leading to the development of cancer. However, children in principle did not have time to be affected by such factors.
The researchers, in collaboration with other international partners, have shown that DNA rings can disrupt the genetic information of cells, thus causing cancer.
These ring-shaped structures are not new, scientists have known about them for decades. Present in cells, they are however not part of the genetic information stored in the form of chromosomes, which is why we speak of extrachromosomal circular DNA. However, we knew little about these structures, due to the lack of technology for detailed analysis.
Thanks to an advanced sequencing technique and high-performance bioinformatics algorithms, researchers have produced the first detailed mapping of the circular DNA present in neuroblastoma, a fatal childhood tumour. Their findings led to important discoveries about the development of this cancer.
Neuroblastoma samples studied
The researchers, with the help of their colleagues at the Barcelona Supercomputing Center, studied neuroblastoma tissue samples from 93 children. Among their findings, they found a much higher prevalence and diversity of circular DNA than expected.
The study found that each tissue sample contained an average of 5,000 copies of circular DNA. She also showed that the process by which sections of DNA separate from a chromosome to form circular DNA and then reintegrate them was done in a different place.
Significance of results
According to Anton Henssen, a researcher at the German Cancer Consortium in Berlin, “it can cause cancer if the original sequence of genetic information is disrupted.”
The researcher, who emphasizes the importance of the research, “the detailed processes involved in this phenomenon have never been studied so deeply before. This study helps to understand how even children’s cells turn into cancerous cells. We were also able to show that certain types of circular DNA can accelerate the growth of neuroblastomas. Testing for their presence could therefore make it easier to predict the course of the disease.”
The study could also provide insights into similar previously unrecognized mechanisms in more complex adult cancers, which could change treatment and clinical outcomes for a wide range of tumors.
The researchers now want to conduct a follow-up study, verify the diagnostic validity of circular DNA and investigate its origins to understand why children develop cancer.
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