DNA mutations can reduce the risk of death in people with bowel cancer

Mutations in the DNA of cellular energy ‘factories’ increase the chances of survival of people with bowel cancer, according to a study published today (Thursday) in Natural metabolism.

Researchers funded by Cancer Research UK found that patients with colon cancer, a common form of bowel cancer, had a 57 to 93% reduced risk of dying from cancer, depending on the presence and type of mitochondrial DNA mutations in their tumors.

The researchers hope that in the future, doctors could use this information to identify patients with more aggressive forms of bowel cancer so they can get the most effective treatments.

Although most of our DNA is wrapped in the center of our cells in the nucleus, we also have some of them in the mitochondria, which are small structures found in our cells that help us convert carbon fuels, such as sugar, into energy. Just as our main nuclear DNA can accidentally get errors in it or ‘mutations’, the same can happen with DNA in our mitochondria.

Mitochondrial mutations are known to be found in cancer cells, but there is little research on what they do or whether they have any effect on the response to treatment or how the cancer will progress.

To answer these questions, researchers at the UK’s Beatson Cancer Research Institute in Glasgow collaborated with the Memorial Sloan Kettering Cancer Center in New York City to collect and analyze data from the largest published set of tumor samples including mitochondrial genome data and related clinical outcomes of the patient.

By analyzing these data from 344 patients with a common form of bowel cancer known as colon cancer, the researchers could match the groups of mutations with the probability of survival.

They found that, after controlling for other variables affecting cancer risk such as age, the presence of mitochondrial mutations was associated with a 57 to 93% reduced risk of death from colon cancer, depending on the type of mitochondrial DNA mutation.

The team also wanted to know how much wider the mitochondrial mutations in cancer are. They used state-of-the-art genetic techniques to look at existing data from over 10,000 tumor samples in 23 types of cancer to look for mitochondrial mutations that recurred frequently.

They found that mitochondrial mutations were present in nearly 6 of 10 tumor samples, and 25 of the 30 most commonly mutated genes across cancer were present in the mitochondrial genome.

These results suggest that mitochondrial mutations could play a role in survival after bowel cancer. Further research is needed to understand the broader implications of mitochondrial mutations on various cancers and to get into the biological underlying behind it.

This new study sheds light on the impact of mitochondrial DNA mutations on cancer, which has been overlooked for decades. This finding could have a huge impact on patient care, with potential changes in the proposed treatment and patient outlook based on the mitochondrial DNA status of their cancer. However, further research will be needed to move these findings from the laboratory to the clinic. “

Dr Payam Gammage, co-lead author of the study and group leader, Cancer Research UK Beatson Institute

Dr Ed Reznik, co-director of the Sloan Kettering Memorial Cancer Center, said: “Using apparently hidden data, we have shown that a critical part of the machine cell for energy production is often broken in cancer. This now begs the question of how these mutations within mitochondrial DNA could be used as a target drug. “

Michelle Mitchell, CEO of Cancer Research UK, said: “This paper highlights how much more needs to be discovered about the inner workings of cancer and all those discoveries for people with cancer that have yet to be unlocked.

Amazing things can be achieved through research, and the benefits are even greater when we work with world-class institutes like the Memorial Sloan Kettering Cancer Center. We look forward to seeing where this relatively unexplored area of ​​research leads us, which could have fantastic potential for people with cancer. “


Journal reference:

Gorelick, AN, and others. (2021) The respiratory complex and tissue lineage trigger repetitive mutations in tumor mtDNA. Natural metabolism. doi.org/10.1038/s42255-021-00378-8.