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Study shows ‘signature’ that radiation damage leaves in our DNA

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by In collaboration with PA Media Group | News

13 September 2016

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DNA helix

A new study has shed light on exactly how a certain type of radiation damages human DNA, raising the risk of cancer.

These mutational signatures could be a diagnosis tool for both individual cases and for groups of cancers” – Professor Adrienne Flanaghan, UCL

The research by the Wellcome Trust Sanger Institute and others – published in Nature Communications – identified two characteristic patterns of DNA damage, caused by ionising radiation, in human cancers.

Professor David Phillips, a Cancer Research UK expert in the environmental causes of cancer who was not involved in the research, said the study was important and that it “helps us understand how some tumours develop.” 

“The researchers read all the genetic information inside cancer cells to pick up DNA ‘signatures’ left behind by ionising radiation, which can cause many different types of cancer,” he added. 

Scientists have known for some time that exposure to ionising radiation, like gamma rays and X-rays, raises a person’s risk of cancer by introducing faults into a cell’s DNA. In the UK, an estimated two per cent of cancer cases are linked to ionising radiation exposure.

A major cause of these cancers is exposure to medical radiation used for the diagnosis and treatment of disease, particularly cancer. This can lead to tumours forming later in life that are distinct from the original disease. 

But how precisely this type of radiation damages our cell’s DNA was unknown. 

The Sanger team looked for patterns, or signatures of DNA changes in 12 human tumours that were associated with exposure to ionising radiation. These samples were then compared with 319 tumours from patients who hadn’t been exposed to radiation. 

After discovering the two distinct DNA signatures for radiation damage that were independent of the type of cancer, the team compared the findings with prostate cancers that had or had not been exposed to radiation. They found the same signatures again. 

Cancer Research UK’s Professor Phillips added that pinpointing these signatures could help doctors settle on the cause of particular cancer.

“Spotting these signatures could help show that radiation has caused a particular tumour and rule out other causes of the disease,” he said.

One of the signatures involves a small number of DNA ‘letters’ being cut out and removed. 

The second is where a piece of DNA has been cut out, spun around, and slotted back in the same place but back to front. This kind of damage doesn’t happen naturally in the body, but radiation could cause enough DNA breaks at the same time to make it possible.

Dr Sam Behjati, clinician researcher at the Sanger Institute and the Department of Paediatrics, University of Cambridge, said: “Showers of radiation chop up the genome causing lots of damage simultaneously. This seems to overwhelm the DNA repair mechanism in the cell, leading to the DNA damage we see.”

Professor Adrienne Flanagan, a collaborating cancer researcher from University College London and Royal National Orthopaedic hospital, said: “These mutational signatures could be a diagnosis tool for both individual cases, and for groups of cancers, and could help us find out which cancers are caused by radiation. 

“Once we have better understanding of this, we can study whether they should be treated the same or differently to other cancers.

Behjati, S. et al. (2016) Mutational signatures of ionizing radiation in second malignancies. Nature Communications. 7.