Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?
Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?
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DOI：
10.1186/s13073-014-0121-3
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发表时间：
2014
期刊：
影响因子：
12.3
通讯作者：
Cook-Deegan R
中科院分区：
文献类型：
--
作者：
Cheon JY;Mozersky J;Cook-Deegan R
经过20年的基因检测和研究，BRCA 1和BRCA 2基因是人类基因组中最具特征的两个基因。因此，不确定意义的变异（VUS;也称为未知意义的变异）的报告频率低于研究不太彻底的基因。然而，VUS仍然未被发现，即使是BRCA 1/2。多基因组和全基因组和全外显子组测序的使用越来越多，将导致更高的VUS检测率，因为更多的基因正在被测试，大多数基因组位点的特征远不如BRCA 1/2。在这篇文章中，我们提请注意道德和政策相关的问题，将出现。从BRCA 1/2检测中获得的经验是对在其他基因检测环境中检测VUS的挑战的有用介绍，而BRCA 1/2独特的特征表明BRCA经验与临床护理中多基因组当前挑战之间的关键差异。我们提出了研究和政策制定的路线，强调将数据汇集到一个集中的开放访问数据库中存储基因变异以改善VUS解释的重要性。此外，为共享和管理数据、分析算法、解释框架和患者再接触建立道德规范和规范做法也是重要的政策领域。本文的在线版本（doi：10.1186/s13073-014-0121-3）包含补充材料，可供授权用户使用。
After two decades of genetic testing and research, the BRCA1 and BRCA2 genes are two of the most well-characterized genes in the human genome. As a result, variants of uncertain significance (VUS; also called variants of unknown significance) are reported less frequently than for genes that have been less thoroughly studied. However, VUS continue to be uncovered, even for BRCA1/2. The increasing use of multi-gene panels and whole-genome and whole-exome sequencing will lead to higher rates of VUS detection because more genes are being tested, and most genomic loci have been far less intensively characterized than BRCA1/2. In this article, we draw attention to ethical and policy-related issues that will emerge. Experience garnered from BRCA1/2 testing is a useful introduction to the challenges of detecting VUS in other genetic testing contexts, while features unique to BRCA1/2 suggest key differences between the BRCA experience and the current challenges of multi-gene panels in clinical care. We propose lines of research and policy development, emphasizing the importance of pooling data into a centralized open-access database for the storage of gene variants to improve VUS interpretation. In addition, establishing ethical norms and regulated practices for sharing and curating data, analytical algorithms, interpretive frameworks and patient re-contact are important policy areas. The online version of this article (doi:10.1186/s13073-014-0121-3) contains supplementary material, which is available to authorized users.
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影响因子：
9.8
作者：
Easton, Douglas F.;Deffenbaugh, Amie M.;Goldgar, David E.
通讯作者：
Goldgar, David E.
DOI：
10.1038/gim.2013.73
发表时间：
2013-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.8
作者：
Caulfield T;Evans J;McGuire A;McCabe C;Bubela T;Cook-Deegan R;Fishman J;Hogarth S;Miller FA;Ravitsky V;Biesecker B;Borry P;Cho MK;Carroll JC;Etchegary H;Joly Y;Kato K;Lee SS;Rothenberg K;Sankar P;Szego MJ;Ossorio P;Pullman D;Rousseau F;Ungar WJ;Wilson B
通讯作者：
Wilson B
影响因子：
9.7
作者：
Jha, Ashish K.;DesRoches, Catherine M.;Joshi, Maulik S.
通讯作者：
Joshi, Maulik S.
影响因子：
9.7
作者：
DesRoches, Catherine M.;Charles, Dustin;Jha, Ashish K.
通讯作者：
Jha, Ashish K.