The researchers from the Wellcome Trust Sanger Institute and their collaborators have been able to identify two characteristic patterns of DNA damage in human cancers, caused by ionising radiation. These patterns may now enable the doctors to identify which tumors have been caused by radiation, and investigate if they should be treated differently. The results are published in Nature Communications and will help to explain how radiation can cause cancer.
Ionising radiation, such as gamma rays, x-rays and radioactive particles can damage the DNA and cause cancer. It is not known how this happens or how many tumors are caused by radiation damage. It has been previously revealed that DNA damage often leaves a molecular fingerprint call a mutational signature, on the genome of a cancer cell. Mutational signatures have been looked at by the researchers in 12 patients with secondary radiation-associated tumors, comparing these with 319 that had not been exposed to radiation.
Dr. Peter Campbell led the study and said “To find out how radiation could cause cancer, we studied the genomes of cancers caused by radiation in comparison to tumours that arose spontaneously. By comparing the DNA sequences we found two mutational signatures for radiation damage that were independent of cancer type. We then checked the findings with prostate cancers that had or had not been exposed to radiation, and fund the same two signatures again. These mutational signatures help us explain how high-energy radiation damages DNA.”
A deletion where small numbers of DNA bases are cut out is one mutational signature. A second one is called a balanced inversion and the DNA is cut in two places, the middle piece spins round, and is joined back again in the opposite orientation. Balanced inversions do not happen naturally in the body, but high-energy radiation could provide enough DNA breaks at the same time to make this possible.
A clinical researcher at the Sanger Institute and the Department of Paediatrics of the University of Cambridge says that this is the first time that scientists have been able to define the damage caused to DNA by ionizing radiation. Mutational signatures could be a diagnosis tool for both individual cases, as well as for groups of cancers. These could help us find out which cancers are caused by radiation and, after we have a better understanding of this, we can study if they should be treated the same or differently to other cancers.
-Dr Fredda Branyon