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.

中文翻译：

---

CDH1 的多基因面板测试：三思而后行。


多基因面板测试（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进以及成本的降低，越来越多的人正在接受 MGPT 进行遗传评估。当包含在 MGPT 中时值得特别考虑的一个基因是 CDH1，它编码细胞间粘附蛋白 E-钙粘蛋白。 CDH1 的致病性和可能致病性种系变异与遗传性弥漫性胃癌综合征相关，在高渗透率家族中，检测这些变异对于正确的风险管理至关重要。然而，最近的数据表明，未经选择的 CDH1 携带者的胃癌外显率可能低于预期。使问题进一步复杂化的是缺乏有效的胃癌筛查策略以及对 CDH1 携带者进行降低风险的全胃切除术的建议。因此，当通常不会仅根据个人或家族史考虑进行 CDH1 检测时，在多基因组检测中发现意外致病性或可能致病性 CDH1 变异，会给患者和提供者带来困境。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 变异可能性的预测试咨询的重要性。尽管 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，个人和提供者需要意识到意外 CDH1 变异的可能性。