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‘Death clock’ in cells can tell you when you will get cancer

Some mutations seem to accumulate at a constant rate year by year

How fast we age and whether we get cancer may be predetermined by two “clocks” discovered in almost every cell in the human body.

Each tick of these clocks is a DNA mutation, and these build up at a constant rate throughout your life. The discovery will give us a deeper understanding of the causes of cancer and an insight into healthy ageing. Not only that, but if you could slow the rate at which these clocks tick, it might be possible to alter the rate at which cancer spreads — and even the rate at which we age.

Rate of gene mutation
Every cell in the body contains DNA, which acquires gene mutations over time. These mutations can sometimes occur in bursts — for example, as a result of smoking or overexposure to the sun. Or they can build up slowly over decades.

Some mutations seem to accumulate at a constant rate year by year, causing DNA damage that can lead to cancer. Now, Michael Stratton at the Wellcome Trust Sanger Institute in Cambridge, UK, and his colleagues have identified two such mutational clocks in almost every cell in the body. They have also figured out how fast these clocks tick in different tissues.

The team started by studying the DNA sequences of more than 10,000 individual cancers, encompassing 36 different types. An algorithm allowed them to search the cancer genomes for complex patterns of mutations called signatures.

Like clock-work
They discovered more than 30 different signatures. They then identified which of these occur in a clock-like manner, with mutations appearing at a steady rate. Two signatures — numbers one and five — fitted the bill. Stratton showed that the clock began in healthy tissue before it became cancerous. “The cancer tissues are the cracked and dirty lens that allow us to look back in time to look at what’s been happening in normal cells,” he says.

The team believes signature one is a “mitotic clock”, a mutation that occurs as a result of cell division. “The rate of mutations correlates with the rate of cell turnover in tissues. So in 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.”

Far less is known about signature five. Preliminary hypotheses suggest it may be linked to DNA repair. Over time, DNA gets damaged and has to be patched up. Signature five might be the outcome of that.

For both signatures, the number of mutations correlated with the age of the person that the sample came from — the older they were, the more they had accumulated. This helped the team figure out how fast the clocks were ticking in each tissue. For instance, signature one ticked quickest in stomach and colon cells, which resulted in about 23 mutations per cell a year, and slowest in breast and ovarian cells, which had three to four mutations a year.

Source: www.newscientist.com

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