An analysis of thousands of tumors from NHS patients has identified a ‘treasury of new clues’ about the causes of cancer.
In the largest study of its kind, researchers at Cambridge University Hospitals looked at the genomes of more than 12,000 people living with cancer in England.
They observed 58 new patterns in their DNA, called mutational signatures, suggesting that there are causes that scientists do not yet know about.
The researchers hope that this discovery will help future studies to trace the root of these cancer-causing mutations.
Before the new discovery, scientists only knew about 51 mutational signatures, including those caused by smoking or UV light.
Identifying these signatures allows doctors to look at each patient’s tumor and match it to specific treatments and drugs.
However, the pattern can only be detected in cancer patients who have had their entire genome sequenced by scientists – which is not routinely done.
Genomics expert Professor Serena Nick-Zainal, who led the study, said these patterns are like ‘fingerprints at the crime scene’.
He said the findings could indicate an ‘Achilles heel’ in individual cancers that could be targeted with treatments.
Researchers from the University of Cambridge studied the genetic makeup of more than 12,000 people with cancer in England, which allows them to see the origins of tumors. They found 58 new patterns in the cancer’s DNA, suggesting there are reasons scientists don’t know yet.
About 375,000 new cancer cases are diagnosed each year in the UK, compared to 1.7 million confirmed in the US.
Cancer is caused by mutations in the genome of cells, which cause the cells to grow out of control until they become tumours.
The latest study, published in the journal Science, analyzed the whole genomes of 12,222 NHS cancer patients in England as part of the 100,000 Genomes Project.
Genome sequencing looks at all the thousands of DNA building blocks within each tumor, showing the mutations that contribute to each individual’s cancer.
Some of the new mutation patterns observed were present in many different cancer patients, while some were more rare.
A finite amount of mutational processes are believed to occur in cancer, prompting the search to identify them all and what causes them.
Knowing the signatures present within a tumor helps to pinpoint their root cause and indicates whether the mutation was caused by environmental factors or a genetic problem.
Professor Nick-Zanel told MailOnline: ‘I sometimes use the analogy of footprints in the sand where the reciprocal signatures are footprints.
‘When you look across a beach, there can be footprints everywhere (similar to cancer, mutations look kinda random, they’re everywhere).
‘But if you study the footprints in detail, there are features that tell you whether the footprints are animal or human.’
She said: ‘Mutational signatures are like those footprints. By studying the mutation pattern in detail, we can start to find out whether something is due to external or cellular factors.’
The researchers used their findings to develop an algorithm called Signature Fit Multi-Step (FitMS) that can spot mutational signatures in new cancer genome samples.
Only patients whose cancers have had their complete genome sequenced will be able to benefit from this tool, but the team believes it could be introduced ‘very early’ for them.
As it stands, only cancers in children, specific leukemias and sarcomas – rare cancers affecting body tissue – are indexed through the NHS, but experts expect this list to expand in the coming years. Will happen.
FitMS will discover mutational signatures in these patients’ cancers, which scientists hope will accelerate their ability to match them with more specific treatments.
Professor Nick-Zainal said: ‘Identifying mutational signatures is important because they are like fingerprints at a crime scene – they help identify the perpetrators of cancer.
‘Some mutational signatures have clinical or treatment implications – they may highlight abnormalities that can be targeted with specific drugs or indicate a potential “Achilles heel” in individual cancers.’
Michelle Mitchell, chief executive of Cancer Research UK, said: ‘This study shows how powerful whole genome sequencing tests are in providing clues to how cancer may develop, how it will behave and which treatment options will work best. can be.’
He said the results ‘could potentially be used within the NHS to improve treatment and care for people with cancer’.
Professor Matt Brown, Chief Scientific Officer of Genomics England, said applying mutational signals to patients could ‘improve the diagnosis and management of cancer patients’.
