https://www.nature.com/articles/d41586-022-01095-2 Skip to main content Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Advertisement Advertisement Nature * View all journals * Search * My Account Login * Explore content * About the journal * Publish with us Subscribe * Sign up for alerts * RSS feed 1. nature 2. news 3. article * NEWS * 21 April 2022 Trove of tumour genomes offers clues to cancer origins Largest-ever study uncovers patterns of mutations that might pinpoint cancer's causes. * Heidi Ledford 1. Heidi Ledford View author publications You can also search for this author in PubMed Google Scholar * Twitter * Facebook * Email You have full access to this article via your institution. Download PDF Coloured scanning electron micrograph of lung cancer cells A lung cancer cell. Identifying mutational signatures associated with specific cancers could eventually lead to more tailored treatments. Credit: Anne Weston, EM STP, The Francis Crick Institute/Science Photo Library By sifting through hundreds of millions of mutations lurking in the genomes of more than 12,000 tumours, researchers have identified patterns of DNA changes that could offer clues to the genetic and environmental causes of cancer. The study, published in Science on 21 April^1, is the largest of its kind. It adds dozens of entries to the growing catalogue of 'mutational signatures' that accompany cancer, and could, in some cases, help clinicians to select the best treatments for individuals. [d41586-022] Huge genetic-screening effort helps pinpoint roots of breast cancer Size matters for these analyses, says Nuria Lopez-Bigas, a computational cancer biologist at the Institute for Research in Biomedicine in Barcelona, Spain. The new work has revealed rare mutational patterns that could not have been picked out from smaller data sets. "When you have this number of whole genomes, you have more power and can make a more complete set of mutational signatures," she says. "It is still early days, but it has a lot of potential in diagnosis and to understand how these tumours have been created." Mutational footprints An individual cancer cell can contain hundreds of thousands of mutations, sometimes more than one million, but only a handful of these will contribute directly to the development of a tumour. For years, researchers have been trawling through genomic data in search of these cancer drivers, in the hope that they could point to new therapies. The many remaining 'bystander' mutations can also be informative. Some cancer-causing agents create characteristic patterns of DNA changes. Ultraviolet light, for example, can cause a DNA base, or 'letter', called cytosine to be replaced by another called thymine at certain sites in the genome. Such changes are often found in melanomas. These patterns of mutations can be likened to footprints on a sandy beach, says Serena Nik-Zainal, a computational biologist at the University of Cambridge, UK, and a co-author on the Science study. "The footprints may look random, but they are not -- they are occurring for a very particular reason," she says. "You would be able to distinguish a human from an animal, a dog from a bird, even an adult from a child and whether they were walking or running." The largest previously reported study of mutational signatures was published in 2020 and analysed about 5,000 whole-genome sequences from tumour samples collected in an international effort^2. [d41586-022] Cancer 'moonshot' has lofty new goal: halve deaths in 25 years In the new study, the team analysed more than 12,000 cancer genomes collected by the UK National Health Service as part of the Genomics England 100,000 Genomes Project. The researchers then used previously published data sets to verify their findings. This involved developing new analytical tools and an algorithm capable of handling hundreds of thousands of mutations, says Andrea Degasperi, a computational biologist at the University of Cambridge and a co- author on the study. The work -- which included samples from 19 tumour types -- yielded dozens of previously unknown mutational footprints, some of which could be traced back to defects in specific cellular methods for repairing DNA. Researchers have probably now found all of the most common mutational signatures, says David Szuts, a cancer biologist at the Research Centre for Natural Sciences in Budapest. "It seems unlikely that the major processes are missed at this point," he says. But the hunt for rare signatures that occur in less than 1% of tumours in a given organ will probably continue as cancer-genome projects flourish worldwide. In addition to searching for further mutational signatures, Degasperi hopes to be able to track down the origins of the more mysterious ones that have not yet been linked to a cancer-causing event. He also wants to investigate other kinds of genetic change: the current study focuses on changes to between one and three DNA letters, but DNA sequences can also be deleted, inserted or rearranged in larger chunks. The hope is that these studies will eventually lead to cancer treatments that are tailored to individual people, he says. "When you understand the mechanism, you might understand a possible correlation with a drug." doi: https://doi.org/10.1038/d41586-022-01095-2 References 1. Degasperi, A. et al. Science 376, eable9283 (2022). Article Google Scholar 2. Alexandrov, L. B. et al. Nature 578, 94-101 (2020). PubMed Article Google Scholar Download references Related Articles * [d41586-022] Cancer 'moonshot' has lofty new goal: halve deaths in 25 years * [d41586-022] Highly mutated cancers respond better to immune therapy * [d41586-022] Huge genetic-screening effort helps pinpoint roots of breast cancer * Biological sex shapes tumour evolution across cancer types * Genome studies unlock childhood-cancer clues Subjects * Genomics * Genetics * Cancer Latest on: Genomics Somatic genomic changes in single Alzheimer's disease neurons Somatic genomic changes in single Alzheimer's disease neurons Article 20 APR 22 Are new Omicron subvariants a threat? Here's how scientists are keeping watch Are new Omicron subvariants a threat? 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Download PDF Related Articles * [d41586-022] Cancer 'moonshot' has lofty new goal: halve deaths in 25 years * [d41586-022] Highly mutated cancers respond better to immune therapy * [d41586-022] Huge genetic-screening effort helps pinpoint roots of breast cancer * Biological sex shapes tumour evolution across cancer types * Genome studies unlock childhood-cancer clues Subjects * Genomics * Genetics * Cancer Advertisement Sign up to Nature Briefing An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. Email address [ ] [ ] Yes! Sign me up to receive the daily Nature Briefing email. I agree my information will be processed in accordance with the Nature and Springer Nature Limited Privacy Policy. Sign up * Close Nature Briefing Sign up for the Nature Briefing newsletter -- what matters in science, free to your inbox daily. 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