Radiation's cancer-causing fingerprint lifted from broken DNA
According to the American Cancer Society, ionising radiation, such as that from x-rays and gamma rays, is a known carcinogen. "The lower the exposure is, the smaller the increase in risk," says the agency. "But there is no threshold below which this kind of radiation is thought to be totally safe." Now researchers say that for the first time, they've been able to spot radiation's exact effect on the DNA in cancerous cells, which could help them distinguish which cancers are caused by radiation and perhaps develop cures specific to that form of the disease.
In searching for the distinct fingerprint left behind by radiation in cancer's DNA, a group of researchers from the Wellcome Trust Sanger Institute (WTSI) and other collaborators looked at 12 patients who had secondary tumors caused by radiation treatment versus 319 of them who had not been exposed to therapeutic radiation. They were looking for DNA damage known as a mutational signature in the cancer cells' genomes.
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They found two.
The first showed that tumors associated with radiation had a median extra 201 DNA base deletions than non-radiation-associated tumors.
The second mutation is known as a balanced inversion "where the DNA is cut in two places, the middle piece spins round, and is joined back again in the opposite orientation," according to WTSI.
"Ionising 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," said Sam Behjati, researcher at WTSI and the department of pediatrics at the University of Cambridge who was involved in the research. "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."
The researchers are hopeful that by understanding exactly how radiation leads to cancer and coming up with a way to spot its telltale signs in tumors, better treatment options might eventually be developed.
"This is the first time that scientists have been able to define the damage caused to DNA by ionising radiation," said professor Adrienne Flanagan, a collaborating cancer researcher from University College London and Royal National Orthopaedic hospital. "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."
The group's work was published today in Nature Communications.
Source: Wellcome Trust Sanger Institute