CDH1 on Multigene Panel Testing: Look Before You Leap COMMENT
CDH1 on Multigene Panel Testing: Look Before You Leap COMMENT
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DOI：
10.1093/jnci/djz229
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发表时间：
2020-04-01
影响因子：
10.3
通讯作者：
Domchek, Susan M.
中科院分区：
文献类型：
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作者：
Katona, Bryson W.;Clark, Dana Farengo;Domchek, Susan M.
多基因组合检测（MGPT）已成为临床实践中癌症风险评估的重要组成部分。随着技术和获取途径的改善以及成本的降低，比以往任何时候都有更多的人接受MGPT进行遗传评估。当包含在MGPT中时，一个值得特别考虑的基因是CDH1，它编码细胞-细胞粘附蛋白E-钙粘蛋白。CDH1中的致病性和可能致病的生殖系变异与遗传性弥漫性胃癌综合征相关，在高度渗透的家族中，检测这些变异对于适当的风险管理至关重要。然而，最近的数据表明，胃癌发病率在CDH1携带者可能低于预期。更复杂的问题是缺乏有效的胃癌筛查策略，并建议在CDH1携带者中进行全胃切除术以降低风险。因此，在多基因组检测中发现意外的致病性或可能致病的CDH1变体，当通常不考虑仅基于个人或家族史进行CDH1检测时，为患者和提供者带来了困境。在这篇评论中，我们强调了MGPT上意外CDH1变异的可能性，概述了与这些变异相关的不确定性，并强调了关于意外CDH1变异的可能性的预测试咨询的重要性。虽然CDH1检测通常对临床决策很重要，但当CDH1被纳入MGPT进行癌症风险评估时，个人和医疗服务提供者需要意识到意外CDH1变异的可能性。
Multigene panel testing (MGPT) has become a critical component of cancer risk assessment in clinical practice. As technology and access improve and costs decrease, more individuals than ever are undergoing MGPT for genetic evaluation. One gene that deserves special consideration when included on MGPT is CDH1, which codes for the cell-cell adhesion protein E-cadherin. Pathogenic and likely pathogenic germline variants in CDH1 have been associated with hereditary diffuse gastric cancer syndrome, and in highly penetrant families, testing for these variants is critical for proper risk management. However, recent data demonstrated that gastric cancer penetrance in unselected CDH1 carriers may be lower than expected. Further complicating matters are the lack of effective screening strategies for gastric cancer and recommendation for risk-reducing total gastrectomy in CDH1 carriers. Therefore, the discovery of an unexpected pathogenic or likely pathogenic CDH1 variant on multigene panel testing, when testing for CDH1 would not normally be considered based on personal or family history alone, creates dilemmas for both patients and providers. In this commentary, we highlight the potential for unexpected CDH1 variants on MGPT, outline the uncertainties associated with these variants, and emphasize the importance of pretest counseling regarding the potential for an unexpected CDH1 variant. Although CDH1 testing is often important for clinical decision-making, individuals and providers need to be aware of the potential for an unexpected CDH1 variant when CDH1 is included on MGPT for cancer risk assessment.