Behind every cancer is a pattern of mutations.
Mutations are small changes to the DNA in our cells. Not all mutations will lead to cancer, but if a cell accumulates enough of them, under certain conditions it may begin to divide and multiply uncontrollably, which is how cancer starts.
Some mutations occur randomly, caused by things like mistakes that our cells make when trying to repair damage to our DNA. These mistakes will cause mutations that differ each time.
But others, like those caused by chemicals in tobacco or UV radiation, leave a distinct mark.
These marks are what we call mutational signatures. They’re unique to the carcinogen that caused them, meaning we can recognise them. For example, if we were to look at the DNA of someone who smokes, we would be able to tell which mutations had been caused by tobacco.
Think of it like this: if a cancer cell was a crime scene, mutational signatures would be the fingerprints left by the culprit.
Studying mutational signatures can also give us insight into why certain types of cancer are more common in certain countries, as specific carcinogens may be more prevalent in certain areas.
When we find fingerprints we recognise, we can follow them back to their origin to identify what might have caused that cancer. But in cases when we don’t recognise them, we’ve got even more work to do.
Matching an unknown fingerprint to its culprit is like detective work, but if we can crack the case, we might be able to use the results to prevent more cases of cancer in the future.
Take smoking. It may seem obvious now that it causes cancer, but we didn’t know it until scientists found it’s fingerprints in cases of lung cancer.
So, to give us the best chance of finding new culprits, we need a detective. Or, in this case, a team of them.
Ambition on an epic scale
Mutographs is one of the teams of international researchers funded by Cancer Grand Challenges, the funding initiative we co-founded with the National Cancer Insitute in the US.
Led by Professor Sir Mike Stratton and including researchers in the UK, US and France, Mutographs were funded by Cancer Grand Challenges in 2017 to identify unknown causes of cancer to help prevent more people from developing the disease.
And in the spirit of a grand challenge, they’re not working on a small scale.
They’ve collected samples from more than 5,000 people with bowel, kidney, oesophageal, bladder or pancreatic cancer across 5 continents.
Importantly, these people are from countries with either high or low levels of these cancers. The driving factors behind these sometimes-huge differences in cancer incidence between countries are currently unknown, and Mutographs want to change that.
The team hope to uncover the mutational signatures that are more common in countries with high incidence, and less common in those with low incidence.
From there, they can work to link the signatures with what might be causing them and determine if those causes can be avoided in future to prevent more cancers.
And new research from the team, published today in Nature, is taking us three steps closer.
