Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results.
Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results.
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DOI：
10.1002/humu.20880
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发表时间：
2008-11
期刊：
影响因子：
3.9
通讯作者：
Tavtigian, Sean V.
中科院分区：
文献类型：
--
作者：
Plon, Sharon E.;Eccles, Diana M.;Easton, Douglas;Foulkes, William D.;Genuardi, Maurizio;Greenblatt, Marc S.;Hogervorst, Frans B. L.;Hoogerbrugge, Nicoline;Spurdle, Amanda B.;Tavtigian, Sean V.
癌症易感基因的基因检测现在被广泛应用于临床实践中，以预测癌症的发生风险。一般来说，基于序列的生殖系DNA测试用于确定个体是否携带明显可能扰乱正常基因功能的变化。基因检测可以检测到明显致病的、明显中性的或临床意义不明确的变异。这些变异对诊断实验室和接受检测的临床医生在解释和清楚地将结果的含义呈现给患者方面提出了相当大的挑战。无论是在基因之间还是在实验室之间，似乎都没有一种一致的方法来解释和报告变异的临床意义。临床医生和患者之间可能会产生相当大的混淆，误解可能会导致不适当的临床后果。在本文中，我们回顾了基于序列的基因检测的现状，描述了肿瘤学中使用的其他标准化报告系统，并提出了一个标准化的分类系统，用于癌症易感基因的基于序列的结果。我们建议根据致病的可能性程度，建立一个由五类变异组成的系统。每一类都与临床治疗高危亲属的具体建议相关联，这些建议将取决于综合征。我们建议每个癌症易感综合征的专家小组促进分类方案，并指定适当的监测和癌症管理指南。国际上采用标准化的报告系统应该会提高基于序列的基因测试的临床实用性，以预测癌症风险。
Genetic testing of cancer susceptibility genes is now widely applied in clinical practice to predict risk of developing cancer. In general, sequence-based testing of germline DNA is used to determine whether an individual carries a change that is clearly likely to disrupt normal gene function. Genetic testing may detect changes that are clearly pathogenic, clearly neutral or variants of unclear clinical significance. Such variants present a considerable challenge to the diagnostic laboratory and the receiving clinician in terms of interpretation and clear presentation of the implications of the result to the patient. There does not appear to be a consistent approach to interpreting and reporting the clinical significance of variants either among genes or among laboratories. The potential for confusion among clinicians and patients is considerable and misinterpretation may lead to inappropriate clinical consequences. In this article we review the current state of sequence-based genetic testing, describe other standardized reporting systems used in oncology and propose a standardized classification system for application to sequence based results for cancer predisposition genes. We suggest a system of five classes of variants based on the degree of likelihood of pathogenicity. Each class is associated with specific recommendations for clinical management of at-risk relatives that will depend on the syndrome. We propose that panels of experts on each cancer predisposition syndrome facilitate the classification scheme and designate appropriate surveillance and cancer management guidelines. The international adoption of a standardized reporting system should improve the clinical utility of sequence-based genetic tests to predict cancer risk.
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