Prostate cancer may be caused by a variety of factors, and sometimes the cause can inform the treatment. Recently researchers from the Wellcome Trust Sanger Institute and their colleagues were able to decode two characteristics of DNA damage caused by ionizing radiation in cancerous prostates. As a result, we are now able to discern which tumors were caused by radiation and adapt our treatment accordingly. Even more exciting, the research is giving us new insights into how radiation cases cancer.
The team published their results in Nature Communications.
We've known for a while how ionizing radiation – gamma rays, x-rays, and certain radioactive particles – can cause cancer by damaging DNA. How this occurs, and which tumors in a cluster were radiation-generated and which arose from other sources, had been a mystery until this new work by the Wellcome Trust Sanger Institute. We also knew that the DNA damage imprinted a “fingerprint” at the molecular level (called a “mutational signature”) on the genome of a cancer cell, but we were unable to connect the dots between the type of radiation and the imprint.
The study involved 12 patients with secondary radiation-associated tumors, and 319 that had not been exposed to radiation.
Dr. Peter Campbell, who led the study, said "To find out how radiation could cause cancer, we studied the genomes of cancers caused by radiation in comparison to tumors 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 found the same two signatures again. These mutational signatures help us explain how high-energy radiation damages DNA."
The hallmark of one of these signature is the empty space where small numbers of DNA bases are deleted. The second mutational signature, described as a “balanced inversion,” occurs when DNA is bisected, the center piece rotates, and is joined back again in the opposite direction. Fortunately for the investigators, balanced inversions do not occur naturally in the body, but sufficiently high-energy radiation could create enough DNA breaks simultaneously to make this possible.
Professor Adrienne Flanagan, a collaborating cancer researcher from University College London and Royal National Orthopaedic hospital, said, "This is the first time that scientists have been able to define the damage caused to DNA by ionizing radiation. 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.”