Proposed framework for triage of putative germline variants detected via tumour genomic testing in UK oncology practice.

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Terri Patricia McVeigh, Helen Hanson, George J Burghel, Clare Turnbull, Katie Snape
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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.

在英国肿瘤学实践中,通过肿瘤基因组测试检测到的假定种系变异的分类建议框架。
在英国,大多数患者通过国民健康服务(NHS)接受公共资助的医疗服务,该服务为符合条件的癌症患者提供肿瘤和/或生殖系检测,以告知临床管理。对肿瘤来源的DNA进行检测可以识别出假定的遗传变异,对先证者及其更广泛的家族有影响,但当怀疑遗传癌症易感性时,这并不是种系基因检测的可靠替代品。通过肿瘤检测确定的变异是生殖系起源的可能性取决于多种临床和技术因素。某些基因型显著影响患者的癌症风险,对这些携带者进行干预可能有助于癌症预防或早期发现,而其他基因型与较低的癌症风险相关,在这种情况下进行相关干预的临床效用有限。我们召集了一次全国临床癌症遗传学和科学研究会议,以使通过基于肿瘤的检测确定的变体的生殖系后续检测合理化。在对比了潜在的方法后,作者同意并完善了nhs背景下的“中间保守”方法的实施,最终的途径再循环到英国临床和科学界,以达成共识并发表。我们概述了相关的患者、遗传和技术考虑因素,告知变异的可能起源,对当前相关指南和NHS实验室实践的回顾,以及实验室和临床团队对需要进行生殖系随访的肿瘤检测变异进行分类的工作流程。该方法旨在将有限的资源用于识别与最大潜在临床影响相关的种系变异,以支持更有效和公平地提供肿瘤基因组医学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
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.
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