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Big genetic study reveals new clues to the causes of cancer

Cambridge analysis of more than 12,000 tumours from NHS patients has found DNA evidence of more than 50 new potential causes of cancer.

DNA analysis of thousands of tumours from NHS patients has found a ‘treasure trove’ of clues about the causes of cancer, with genetic mutations providing a personal history of the damage and repair processes each patient has been through.

In the biggest study of its kind, a team of scientists led by Professor Serena Nik-Zainal from Cambridge University Hospitals (CUH) and University of Cambridge, analysed the complete genetic make-up or whole-genome sequences (WGS) of more than 12,000 NHS cancer patients.

Watch video: Prof Serena Nik-Zainal explains what the study found


Video transcript

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So this is the largest

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study of its kind of whole genome sequence to human cancers.

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That means that every single

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DNA building block has been sequenced in these cancers,

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and we have utilised the data that has been generated

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by Genomics England with the 100,000 genomes project.

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Some 12,000 cancers have been sequenced, and we were able to look at all

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the mutations that have arisen in each of these cancers.

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So that's thousands and thousands of mutations

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and that gives us a lot of power to be able to look at patterns across

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patient samples.

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What we identified were 58 new mutation patterns,

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some of these patterns occur frequently across many different patients,

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or they’re common, and some of them are rare and more individual to each patient.

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An additional

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feature that we have developed in this study is to develop a tool

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to enable users to use this new information,

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so we've gone a step further, we haven't just identified new things,

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we’ve created a tool, that will help clinical users as well as scientific users

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to utilise this new information in order to diagnose

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and to treat patients more effectively.

Because of the vast amount of data provided by whole genome sequencing, the researchers were able to detect patterns in the DNA of cancer or ‘mutational signatures’, that provide clues about whether a patient has had a past exposure to environmental causes of cancer such as smoking or UV light, or has internal, cellular malfunctions.

The team were also able to spot 58 new mutational signatures, suggesting that there are additional causes of cancer that we don't yet fully understand.

A graphic showing DNA
Whole genome sequencing of 12,000 tumours revealed new mutational patterns

WGS gives us a total picture of all the mutations that have contributed to each person’s cancer.

Dr Andrea Degasperi, University of Cambridge

Dr Degasperi, research associate at the University of Cambridge and first author, said:

"With thousands of mutations per cancer, we have unprecedented power to look for commonalities and differences across NHS patients, and in doing so we uncovered 58 new mutational signatures.

"Some of these are common patterns while others are rare, but they may have important clinical or treatment implications".

National Genomic Test Directory
Samples being processed in an NHS geomics lab in Cambridge

This study could not have been carried out without the generous contribution of samples from patients and clinicians throughout England.

Serena Nik-Zainal, honorary consultant in clinical genetics at CUH

Serena Nik-Zainal, a professor of genomic medicine and bioinformatics at the University of Cambridge and an honorary consultant in clinical genetics at CUH said:

“The reason it is important to identify mutational signatures is because they are like fingerprints at a crime scene - they help to pinpoint cancer culprits.

"Some mutational signatures have clinical or treatment implications – they can highlight abnormalities that may be targeted with specific drugs or may indicate a potential ‘Achilles heel’ in individual cancers.

"We were able to perform a forensic analysis of over 12,000 NHS cancer genomes thanks to the generous contribution of samples from patients and clinicians throughout England.

"We have also created FitMS, a computer-based tool to help scientists and clinicians identify old and new mutational signatures in cancer patients, to potentially inform cancer management more effectively.”

Michelle Mitchell, chief executive of Cancer Research UK, said:

“This study shows how powerful whole genome sequencing tests can be in giving clues into how the cancer may have developed, how it will behave and what treatment options would work best.

"It is fantastic that insight gained through the NHS 100,000 Genomes Project can potentially be used within the NHS to improve the treatment and care for people with cancer.”

Professor Matt Brown, chief scientific officer of Genomics England said:

“Mutational signatures are an example of using the full potential of WGS. We hope to use the mutational clues seen in this study and apply them back into our patient population, with the ultimate aim of improving diagnosis and management of cancer patients.”

Prof Dame Sue Hill, chief scientific officer for England and senior responsible officer for genomics in the NHS said:

“The NHS contribution to the 100,000 Genomes Project was vital to this research and highlights how data can transform the care we deliver to patients, which is a cornerstone of the NHS Genomic Medicine Service.”

This research was supported by Cancer Research UK and published today in the journal Science here: (opens in a new tab)

The genomic data was provided by the 100,000 Genomes Project (opens in a new tab) an England-wide clinical research initiative to sequence 100,000 whole genomes from around 85,000 patients affected by rare disease or cancer.

The study was supported by the NIHR Cambridge Biomedical Research Centre.