Study reveals clues to cancer causes and potential for personalised treatment for patients

Mutational signatures in tumours have been described as ‘like fingerprints at a crime scene’, reports Lamiat Sabin

Patterns in the DNA of cancers would be able to show if smoking caused the disease in a patient (PA Archive)

Scientists claim to have found clues about the causes of cancer which they say could lead to personalisation of treatments for the disease.

After analysing tumours of 12,000 NHS patients, researchers said that it was possible for the first time to detect patterns – called mutational signatures – in the DNA of cancers.

These patterns serve as clues including whether a patient has had past exposure to contributing factors such as smoking or UV light.

These signatures would allow doctors to match specific treatments and medications to a cancer patient, researchers said.

The patterns can only be detected through the analysis of the vast amounts of data gleaned from whole genome sequencing, a process which identifies the genetic make-up of a cell.

Principal author Serena Nik-Zainal, a professor of genomic medicine and bioinformatics at the University of Cambridge and an honorary consultant in clinical genetics at Cambridge University Hospitals, said: “It’s like looking at a very busy beach with thousands of footprints in the sand. To the untrained eye, the footprints appear to be random and meaningless.

“But if you are able to study them closely, you can learn a lot about what’s been going on, distinguish between animal and human prints, whether it’s an adult or child, what direction they’re travelling in, etc. It’s the same thing with the mutational signatures.

“The use of whole genome sequencing can identify which ‘footprints’ are relevant/important and reveal what’s happened through the development of the cancer.”

In analysing the tumours, researchers spotted 58 new mutational signatures that suggests there are additional causes of cancer that are not yet fully understood.

Prof Nik-Zainal 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.”

Dr Andrea Degasperi, research associate at the University of Cambridge and first author, said: “Whole genome sequencing gives us a total picture of all the mutations that have contributed to each person’s cancer.

“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 and broadened our knowledge of cancer.”

The findings are now being incorporated into the NHS as researchers and clinicians have the use of a digital tool called FitMS that will help them identify the mutational signature and 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.”

The research was supported by Cancer Research UK and published in the journal Science.