Koudová Monika, Puchmajerová Alena
Klin Onkol. 2019 Summer;32(Supplementum2):14-23. doi: 10.14735/amko2019S14.
Expanded gene panel testing for hereditary cancer predispositions using massive parallel sequencing can identify heterozygous pathogenic variants of genes that cause autosomal recessive inherited cancer syndromes. There are no clinical guidelines regarding assessment of the risk of developing solid tumors or for developing appropriate surveillance strategies for heterozygotes for most of these genes, nor is there delineation with respect to the management for genetic testing of relatives and partners. Based on current knowledge, our aim was to create “Czech guidelines” for these cases. Here, we present an overview of the selected genes for autosomal recessive inherited tumor syndromes. The genes were divided into two groups: genes causing Fanconi anemia and genes causing other autosomal recessive inherited tumor syndromes. A summary table was created for each group. The table shows the population frequency of heterozygotes, the cancer risk for heterozygotes, the proposed surveillance strategy, and recommendations for family prediction and genetic testing of partners. Predictive testing should be performed in the case of heterozygotes that have an increased risk of cancer and/or as prerequisite to further reproduction of heterozygotes for a given gene with significant population frequency (this allows an estimation of the risk of autosomal recessive syndrome for children of heterozygote for mutation). These suggestions and recommendations are based on current knowledge and would need to be further corrected in the future based on increasing knowledge of existing or as-yet-unidentified genes. The authors thank to all the staff of the Molecular Genetic Laboratory of the GENNET Medical Genetics and Reproductive Medicine Center for their cooperation. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 21. 3. 2019 Accepted: 2. 5. 2019.
使用大规模平行测序对遗传性癌症易感性进行扩展基因检测，可以识别导致常染色体隐性遗传癌症综合征的基因的杂合致病性变异。对于大多数此类基因，目前尚无关于评估实体瘤发生风险或针对杂合子制定适当监测策略的临床指南，也没有关于亲属和伴侣基因检测管理的明确规定。基于目前的知识，我们的目标是为这些病例制定“捷克指南”。在此，我们概述了常染色体隐性遗传肿瘤综合征的选定基因。这些基因分为两组：导致范可尼贫血的基因和导致其他常染色体隐性遗传肿瘤综合征的基因。为每组创建了一个汇总表。该表显示了杂合子的人群频率、杂合子的癌症风险、建议的监测策略以及对家庭预测和伴侣基因检测的建议。对于癌症风险增加的杂合子，以及作为具有显著人群频率的特定基因杂合子进一步生育的先决条件（这允许估计突变杂合子子女患常染色体隐性综合征的风险），应进行预测性检测。这些建议基于目前的知识，未来需要根据对现有或尚未识别基因的更多了解进行进一步修正。作者感谢GENNET医学遗传学和生殖医学中心分子遗传实验室的所有工作人员的合作。作者声明他们在研究中使用的药物、产品或服务方面没有潜在的利益冲突。编辑委员会声明该手稿符合ICMJE对生物医学论文的建议。提交日期：2019年3月21日 接受日期：2019年5月2日。
