Mutographs

Challenge

Discover how unusual patterns of mutation are induced by different cancer-causing events 

Researchers
8
Principal Investigator
Professor Sir Mike Stratton
Location
UK, France, USA
Funded By
Cancer Research UK - £20m
Specialisms
Genetics, chemistry, bioinformatics, epidemiology

Detective work: searching for unknown causes of cancer   

It’s a cliché, but prevention really is better than cure. By examining the damaging fingerprints left on our DNA by cancer-causing factors, the Mutographs team hopes to identify unknown causes of cancer to help prevent more people from developing the disease.      

Combing for clues

Funded by:

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As a cell goes through life, its DNA picks up a unique pattern of damage. This can be caused by exposure to factors like UV light, from behaviours like smoking or drinking alcohol, or can happen randomly through natural cellular processes. Depending on the amount and type of damage, this can cause a cell to become cancerous.  

Working backwards from this damage can provide clues as to the cause of cancer: each factor will leave a different, distinctive pattern, known as a ‘mutational fingerprint’. For example, cancers caused by UV radiation will have a different fingerprint to those linked to tobacco.   

So far, scientists have uncovered 50 cancer-associated mutational fingerprints. But they can only trace around half of them back to a specific cause. Figuring out what causes the other 25 or so cancer-associated fingerprints could identify new, potentially preventable causes of cancer.   

Taking on this enormous challenge is the Mutographs team, a diverse group of experts from the UK, US and France. Together, they hope to dramatically improve our understanding of what causes cancer and prevent more cases in the future, by helping people reduce their risk of the disease. 

Professor Sir Mike Stratton, Principal Investigator, Mutographs

Director, Wellcome Trust Sanger Institute

Our aim is to help prevent more cancers and reduce the global burden of this disease.

Collecting the evidence

Mutographs’ ambition is of epic scale, with samples collected across 5 continents, from 5,000 people with either pancreatic, kidney, oesophageal or bowel cancer. Importantly, these people are from countries with either high or low levels of these cancers. For example, one type of oesophageal cancer is 10–20 times more common in Iran and East Africa than in other countries.   

But what drives this massive difference? To answer, the team will identify the mutational fingerprint of each sample, before cross-referencing between each cancer type and against countries with high or low levels of the disease.   

The team hopes to determine which fingerprints are more common – or potentially only present – in patients’ samples in countries with high levels of specific cancers, and which are less common – or even absent – in countries with low levels. From here, they’ll study the habits, lifestyles and environments of patients who’ve generously donated their samples, to determine what caused these fingerprints and if these factors could be avoided in future. 

Professor Sir Mike Stratton

Filling in the gaps 

By harnessing the power of discovery, Mutographs could dramatically improve our understanding of what causes cancer. If successful, it could lead to better information for people looking to reduce their own risk of cancer and help inform government policies, making our ability to prevent certain cancers much more effective. 

Detective skills  

As well as working backwards to identify unknown cancer causes, another important aim of Mutographs’ work is to determine whether suspected cancer-causing factors are responsible for specific fingerprints, using animal models and organoids (mini lab-grown organs) made from human cancer cells. The team is also studying people thought to be at risk of cancer to better understand cancer development. 

Professor Sir Mike Stratton, Principal Investigator, Mutographs
Professor Allan Balmain
Dr Ludmil B. Alexandrov
Dr Paul Brennan
Dr Peter Campbell
Professor David Phillips
Mimi McCord
Maggie Blanks