Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Familial Cancer Service, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney Medical School, University of Sydney, Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia.
Mod Pathol. 2017 Aug;30(8):1048-1068. doi: 10.1038/modpathol.2017.20. Epub 2017 Apr 28.
Endometrial cancer is the most common gynecological cancer, but is nevertheless uncommon enough to have value as a signature cancer for some hereditary cancer syndromes. Commercial multigene testing panels include up to 13 different genes annotated for germline DNA testing of patients with endometrial cancer. Many other genes have been reported as relevant to familial endometrial cancer from directed genome-wide sequencing studies or multigene panel testing, or research. This review assesses the evidence supporting association with endometrial cancer risk for 32 genes implicated in hereditary endometrial cancer, and presents a summary of rare germline variants in these 32 genes detected by analysis of quasi-population-based endometrial cancer patients from The Cancer Genome Atlas project. This comprehensive investigation has led to the conclusion that convincing evidence currently exists to support clinical testing of only six of these genes for diagnosis of hereditary endometrial cancer. Testing of endometrial cancer patients for the remaining genes should be considered in the context of research studies, as a means to better establish the level of endometrial cancer risk, if any, associated with genetic variants that are deleterious to gene or protein function. It is acknowledged that clinical testing of endometrial cancer patients for several genes included on commercial panels may provide actionable findings in relation to risk of other cancers, but these should be considered secondary or incidental findings and not conclusive evidence for diagnosis of inherited endometrial cancer. In summary, this review and analysis provides a comprehensive report of current evidence to guide the selection of genes for clinical and research gene testing of germline DNA from endometrial cancer patients.
子宫内膜癌是最常见的妇科癌症，但由于其罕见性，对于某些遗传性癌症综合征来说，它具有作为标志性癌症的价值。商业多基因检测面板包括多达 13 个不同的基因，这些基因被注释为用于子宫内膜癌患者的种系 DNA 检测。许多其他基因已通过定向全基因组测序研究或多基因面板测试或研究报告与家族性子宫内膜癌相关。本综述评估了 32 个与遗传性子宫内膜癌相关的基因的关联证据，这些基因与子宫内膜癌风险相关，并总结了 32 个基因中通过分析癌症基因组图谱项目中的准人群子宫内膜癌患者的种系变异而发现的罕见种系变异。这项全面的研究得出的结论是，目前有令人信服的证据支持对其中仅 6 个基因进行临床检测，以诊断遗传性子宫内膜癌。对于其余基因的检测，应在研究背景下考虑，以更好地确定与基因或蛋白功能有害的遗传变异相关的子宫内膜癌风险水平。需要承认的是，对商业面板上包含的几个基因进行子宫内膜癌患者的临床检测可能会为其他癌症的风险提供可操作的发现，但这些应被视为次要或偶然发现，而不是遗传性子宫内膜癌诊断的确凿证据。总之，本综述和分析提供了当前证据的综合报告，以指导选择用于子宫内膜癌患者种系 DNA 的临床和研究基因检测的基因。
