Clinical application of tumour whole genome sequencing in routine molecular diagnostics for solid cancer patients

Clinical application of tumour whole genome sequencing in routine molecular diagnostics for solid cancer patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical application of tumour whole genome sequencing in routine molecular diagnostics for solid cancer patients E. Cuppen, Jeffrey van Putten, Petur Snaebjornsson, Linda Bosch, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5999963/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Mar, 2026 Read the published version in Nature Medicine → Version 1 posted You are reading this latest preprint version Abstract Molecular testing is increasingly relevant for enabling precision medicine for cancer patients. Whole genome sequencing (WGS) provides a tumour-agnostic solution for the growing complexity of DNA-based biomarker detection, with promising results demonstrated in various studies. Here, we present real-world data of 888 patients to demonstrate the clinical value of routine use of paired tumour-normal WGS-based diagnostics for solid tumours in a comprehensive cancer center setting. WGS was successful in 89% of cases with a median turnaround time of 6 working days. Potentially actionable biomarkers were identified in 74% of patients, including biomarkers for reimbursed and experimental targeted therapies in 30% and 64% of patients, respectively. Importantly, 38% and 24% of these patients did start biomarker-guided therapy within one year. For cancers of unknown primary (n=123), WGS aided in solving diagnosis or identified reimbursed treatment options in 68% of cases, with 70% starting a tumour type-specific treatment after WGS. Finally, clinically relevant pathogenic germline variants were identified in 6.5% of all patients. Together, routine WGS-based diagnostics outperformed previous study results and had clinical consequences in 42% of all patients tested. WGS thus provides a versatile and future-proof test approach for supporting clinical care for patients with solid cancers. Biological sciences/Cancer/Cancer genomics Biological sciences/Cancer/Cancer of unknown primary Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTables16.xlsx Supplementary Tables Cite Share Download PDF Status: Published Journal Publication published 20 Mar, 2026 Read the published version in Nature Medicine → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5999963","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":417442547,"identity":"94899857-7c96-4923-8159-60232e897d63","order_by":0,"name":"E. 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