DNA study uncovers 58 new mutations that trigger cancer

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CAMBRIDGE, United Kingdom — The largest study of whole genome sequencing (WGS) to date has discovered 58 new ways that cancer develops in the human body.

An ultra-detailed examination of thousands of tumors from more than 12,000 cancer patients in the United Kingdom uncovered a “treasure trove” of clues about what causes cancer. The research could eventually help scientists create new treatments for the deadly disease.

University of Cambridge scientists found dozens of “mutational signatures” that provide clues to why people develop cancer in the first place. The data, which found patterns in the DNA of cancer cells, also revealed whether a patient smoked, used tanning beds, or had an internal, cellular malfunction contributing to disease onset.

While the scientists have found the 58 new mutational signatures, they believe these are additional causes of cancer we do not yet fully understand. The data comes from the 100,000 Genomes Project, a UK-wide research initiative supported by Cancer Research UK, which examines thousands of patients affected by rare disease or cancer.

“WGS gives us a total picture of all the mutations that have contributed to each person’s cancer,” says Dr. Andrea Degasperi, a Cambridge research associate in a university release.

“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.”

Mutations are ‘fingerprints at a crime scene’

“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,” adds Serena Nik-Zainal, from the Department of Medical Genetics and an honorary consultant in clinical genetics at Cambridge University Hospitals. “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.”

“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,” explains Michelle Mitchell, chief executive of Cancer Research UK.

“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,” concludes Professor Matt Brown, chief scientific officer of Genomics England.

The study is published in the journal Science.

South West News Service writer Joe Morgan contributed to this report.