Prostate Cancers Linked to Radiation Exposure Carry Mutation Signatures, Study Finds

Prostate Cancers Linked to Radiation Exposure Carry Mutation Signatures, Study Finds

Researchers exploring genetic changes caused by ionizing radiation were able, possibly for a first time, to identify characteristic patterns of DNA mutations in prostate cancer. These patterns may help physicians in identifying tumors caused by exposure to radiation, and in determining if particular treatments are suitable for them.

The study, “Mutational signatures of ionizing radiation in second malignancies,” published in the journal Nature Communications, will also help scientists in studying how ionizing radiation causes cancer.

Ionizing radiation is present in X-rays, gamma-rays, and radioactive particles, and researchers have long known that exposure to such radiation can damage DNA and cause cancer. Despite this, scientists do not know how the DNA damage leads to cancer, or even how many cancers are caused by this type of radiation.

Researchers at the Wellcome Trust Sanger Institute knew that other types of DNA damage, linked to cancer, lead to characteristic molecular changes — so-called mutational signatures. To explore if ionizing radiation also gives rise to such signatures, they studied the genes in tumor tissue from 12 patients with secondary cancers caused by radiation exposure.

They compared these tumors to those of 319 patients who had not been exposed to radiation, and discovered two DNA changes that were typical of the irradiated tissue and did not depend on the type of cancer: one mutation signature was an enrichment in small deletions, where some nucleotides are cut from the DNA; the second was an enrichment in balanced inversions, a rare type of rearrangement where the DNA is cut in two places, and when the middle piece reconnects it does so in the opposite direction.

“We then checked the findings with prostate cancers that had or had not been exposed to radiation, and found the same two signatures again,” Dr. Peter Campbell, the study’s senior author, said in a news release.

“Ionizing radiation probably causes all types of mutational damage, but here we can see two specific types of damage and get a sense of what is happening to the DNA,” added Dr. Sam Behjati, a clinician and researcher at the Sanger Institute and the University of Cambridge, both in the U.K.

According to Adrienne Flanagan, a professor at University College London who also contributed to the study, the newly found signatures could be used to diagnose both individual cancers and groups of cancers, enabling oncologists to learn 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,” said Flanagan.

Still, researchers said that the number of cancers directly caused by radiation exposure is likely low. “The relatively low number of mutations that we directly linked to ionizing radiation may seem surprising for such a well-known carcinogen. It is certainly considerably less than seen for cancers associated with tobacco, sunlight or aristolochic acid exposure,” they concluded. “This probably reflects the fact that although the attributable risk of such cancers is high, the absolute risk is relatively low … [and]  suggests that although ionizing radiation clearly pushes bystander cells in the radiotherapy field towards cancer, the absolute burden of radiation-induced mutations per cell would not be high and additional driver mutations would be required.”

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