Terri Patricia McVeigh, Helen Hanson, George J Burghel, Clare Turnbull, Katie Snape
{"title":"Proposed framework for triage of putative germline variants detected via tumour genomic testing in UK oncology practice.","authors":"Terri Patricia McVeigh, Helen Hanson, George J Burghel, Clare Turnbull, Katie Snape","doi":"10.1136/jmg-2025-110947","DOIUrl":null,"url":null,"abstract":"<p><p>In the UK, most patients receive publicly funded medical care through the National Health Service (NHS), which funds tumour and/or germline testing for eligible patients with cancer to inform clinical management.Testing on tumour-derived DNA may identify putative heritable variants, with implications for the proband and their wider family, but is not a reliable substitute for germline genetic testing when hereditary cancer predisposition is suspected.The likelihood that a variant identified through tumour testing is of germline origin depends on multiple clinical and technical factors. Certain genotypes significantly influence a patient's cancer risk, and intervention in those carriers may facilitate cancer prevention or early detection, while other genotypes are associated with lower cancer risk, and associated intervention in such cases have limited clinical utility.We convened a national meeting of clinical cancer genetics and scientific leads to rationalise germline follow-up testing of variants identified through tumour-based testing. After contrasting potential approaches, implementation of an NHS-contextualised 'intermediate conservative' approach was agreed and refined by the authors, with the final pathway recirculated to the UK clinical and scientific community for consensus agreement and publication.We outline relevant patient, genetic and technical considerations informing likely origin of variants, a review of current relevant guidance and NHS laboratory practices and a workflow for laboratory and clinical teams to triage tumour-detected variants requiring onward germline follow-up. This approach aims to direct limited resources towards identifying germline variants associated with the greatest potential clinical impact, with a view to supporting more efficient and equitable delivery of genomic medicine in oncology.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jmg-2025-110947","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
In the UK, most patients receive publicly funded medical care through the National Health Service (NHS), which funds tumour and/or germline testing for eligible patients with cancer to inform clinical management.Testing on tumour-derived DNA may identify putative heritable variants, with implications for the proband and their wider family, but is not a reliable substitute for germline genetic testing when hereditary cancer predisposition is suspected.The likelihood that a variant identified through tumour testing is of germline origin depends on multiple clinical and technical factors. Certain genotypes significantly influence a patient's cancer risk, and intervention in those carriers may facilitate cancer prevention or early detection, while other genotypes are associated with lower cancer risk, and associated intervention in such cases have limited clinical utility.We convened a national meeting of clinical cancer genetics and scientific leads to rationalise germline follow-up testing of variants identified through tumour-based testing. After contrasting potential approaches, implementation of an NHS-contextualised 'intermediate conservative' approach was agreed and refined by the authors, with the final pathway recirculated to the UK clinical and scientific community for consensus agreement and publication.We outline relevant patient, genetic and technical considerations informing likely origin of variants, a review of current relevant guidance and NHS laboratory practices and a workflow for laboratory and clinical teams to triage tumour-detected variants requiring onward germline follow-up. This approach aims to direct limited resources towards identifying germline variants associated with the greatest potential clinical impact, with a view to supporting more efficient and equitable delivery of genomic medicine in oncology.
期刊介绍:
Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.