Illustration of light blue speckled DNA helix on a dark background
Illustration of light blue speckled DNA helix on a dark background

Study Nearly Doubles Known Cancer-Linked Mutational Signatures

Analyzing the whole genome sequences of more than 18,000 tumors, researchers catalog nearly 60 new patterns of mutations that could inform cancer treatment.

Jef Akst
Jef Akst

Jef Akst is managing editor of The Scientist, where she started as an intern in 2009 after receiving a master’s degree from Indiana University in April 2009 studying the mating behavior of seahorses.

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Apr 22, 2022

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A massive survey of patient genomes has unveiled dozens of mutational signatures associated with various cancer types. The work, published yesterday (April 21) in Science, also includes a new tool to allow clinicians to search for such patterns of mutations in individual cancer patients, something the team argues could point to beneficial therapies.

“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,” University of Cambridge genomicist and bioinformatician Serena Nik-Zainal, an honorary consultant in clinical genetics at Cambridge University Hospitals, tells The Guardian. For example, certain signatures point to tobacco smoking or exposure to ultraviolet radiation as the causative mutagens. “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,” Nik-Zainal says.

“We can really begin to tease out the underpinnings of the erosive sort of forces that go to sort of generate cancer,” MD Anderson Cancer Center’s Andrew Futreal, who was not involved in the study, tells the Associated Press.

The researchers conducted their analysis on samples from 12,222 patients in the 100,000 Genomes Project as well as a few thousand other genomes from existing datasets, for a total of 18,640 genomes across 19 cancer types—the largest set of whole genome sequences to date. In the end, they confirmed 51 of the more than 70 mutation patterns listed in the Catalogue of Somatic Mutations in Cancer (COSMIC) and identified 58 additional signatures.

Dávid Szüts, a cancer researcher at the Institute of Enzymology of the Research Centre for Natural Sciences in Hungary explains in an accompanying perspective article that with hundreds of samples per organ type, the team was able to detect rare signatures that are found in less than 1 percent of patients with cancer in a particular organ. “The palette of common signatures appears to be saturated, but the approach leaves the door open to finding rare signatures,” writes Szüts, who was not involved in the study.

Nik-Zainal and her colleagues also developed a new tool called FitMS to help clinicians and researchers identify mutational signatures in cancer patients. Coauthor Matt Brown, chief scientific officer of Genomics England, the company behind the 100,000 Genomes Project, tells BBC News: “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.”