‘Death Clock’ In Cells Can Tell Doctors When Patients Will Develop Cancer
Inside each of us is a clock that counts down to how fast we'll age and whether or not any genetic mutations will develop into cancer someday. Researchers from the Wellcome Trust Sanger Institute in Cambridge, UK, have discovered two different mutations that accumulate at a constant rate, similar to a ticking clock. The study, published in the journal Nature Genetics, is the first to identify these "death clocks" in nearly every cell in the human body.
"It's not an inevitability for an individual to get cancer, but it's an inevitability for us as a species," the study's lead author Michael Stratton, a researcher at the Wellcome Trust Sanger Institute, told New Scientist. "We accumulate mutations over a lifetime and in some people the correct combination leads to a cancer emerging. The machinery that replicates DNA occasionally makes mistakes and signatures might be the outcome of that."
For the study, researchers studied the DNA sequences of 36 cancers from 10,000 individuals. They searched for signatures in the DNA, or complex patterns an individual cell forms when it mutates. Out of the 30 different signatures discovered, two appeared to build up at a steady rate, like the tick-tock of a clock. One clock represented a person aging, and as the hands of the clock ticked by, cell damage accumulated; the second clock represented how repair mechanisms in the cell worked to fix damaged DNA.
Healthy cells are all programmed to multiply and die at a specific rate. These cells are often repaired by internal mechanisms, but when a mutation occurs, it can multiple uncontrollably to form a tumor. Mutations are caused by damages or changes in the structure of the DNA, which either occur naturally as we age or by a sporadic mutation from overexposure to the sun, smoking, or obesity.
"The rate of mutations correlate with the rate of cell turnover in tissues," Stratton explained. "So in the future we'll be able to use the number of mutations from this signature to know how many times a cell has divided – giving us a deep insight into the biology of human tissues."
Stratton found the first clock ticked faster in stomach and colon cells, adding up to 23 mutations per cell each year. On the other hand, breast and ovarian cells ticked by more slowly with only four mutations each year. When a cell became cancerous, the clocks continued to tick the same mutation pattern; meaning researchers could predict how fast a certain cancer may develop. Not only that, but Stratton believes it may be possible to look at the clocks in healthy cells to predict when a cancer may appear before it presents itself by comparing the mutation rates of people who were once healthy, but later developed cancer.
"Every time we find something that causes cancer we think about how we can reduce it," Stratton said. "Further research will discover if our mutation rates differ between individuals. If that is the case, the expectation would be that those rates could be read out to predict the time they might take to become cancerous."
Source: Stratton MR, Alexandrov LB, Jones PH, et al. Clock-like mutational processes in human somatic cells. Nature Genetics. 2015.