文章：

多基因面板中250名突变携带者亲属的种系突变检测：BRCA1/2以外其他基因致病性变异的影响

Detection of Germline Mutations in a Cohort of 250 Relatives of Mutation Carriers in Multigene Panel: Impact of Pathogenic Variants in Other Genes beyondBRCA1/2

原文发布日期：6 December 2023

DOI: 10.3390/cancers15245730

类型: Article

开放获取: 是

英文摘要：

Background: Several hereditary–familial syndromes associated with various types of tumors have been identified to date, evidencing that hereditary cancers caused by germline mutations account for 5–10% of all tumors. Advances in genetic technology and the implementation of Next-Generation Sequencing (NGS) have accelerated the discovery of several susceptibility cancer genes, allowing for the detection of cancer-predisposing mutations in a larger number of cases. The aim of this study is to highlight how the application of an NGS-multigene panel to a group of oncological patients subsequently leads to improvement in the identification of carriers of healthy pathogenic variants/likely pathogenic variants (PVs/LPVs) and prevention of the disease in these cases. Methods: Starting from a total of 110 cancer patients carrying PVs/LPVs in genes involved in cancer susceptibility detected via a customized NGS panel of 27 cancer-associated genes, we enrolled 250 healthy collateral family members from January 2020 to July 2022. The specific PVs/LPVs identified in each proband were tested in healthy collateral family members via Sanger sequencing. Results: A total of 131 out of the 250 cases (52%) were not carriers of the mutation detected in the affected relative, while 119 were carriers. Of these, 81/250 patients carried PVs/LPVs onBRCA1/2(33%), 35/250 harbored PVs/LPVs on other genes beyondBRCA1andBRCA2(14%), and 3/250 (1%) were PVs/LPVs carriers both onBRCA1/2and on another susceptibility gene. Conclusion: Our results show that the analysis ofBRCA1/2genes would have only resulted in a missed diagnosis in a number of cases and in the lack of prevention of the disease in a considerable percentage of healthy carriers with a genetic mutation (14%).

摘要翻译： 

背景：迄今为止，已发现多种与不同类型肿瘤相关的遗传性家族综合征，表明由生殖系突变引起的遗传性癌症占所有肿瘤的5-10%。基因技术的进步和下一代测序（NGS）的应用加速了多个癌症易感基因的发现，使得在更多病例中检测到癌症易感突变成为可能。本研究旨在强调，将NGS多基因检测应用于一组肿瘤患者，如何有助于提高健康致病性变异/可能致病性变异（PVs/LPVs）携带者的识别率，并在这些病例中实现疾病预防。 方法：自2020年1月至2022年7月，我们从110名通过定制的27个癌症相关基因NGS检测发现携带癌症易感基因PVs/LPVs的癌症患者中，招募了250名健康的旁系亲属。通过桑格测序，对每个先证者中发现的特定PVs/LPVs在其健康旁系亲属中进行检测。 结果：在250例中，共有131例（52%）未携带患病亲属中检测到的突变，而119例为携带者。其中，81/250例（33%）携带BRCA1/2基因的PVs/LPVs，35/250例（14%）携带BRCA1和BRCA2之外其他基因的PVs/LPVs，3/250例（1%）同时携带BRCA1/2及另一个易感基因的PVs/LPVs。 结论：我们的结果表明，仅分析BRCA1/2基因会导致部分病例漏诊，并使相当比例携带基因突变的健康携带者（14%）无法实现疾病预防。

原文链接：

Detection of Germline Mutations in a Cohort of 250 Relatives of Mutation Carriers in Multigene Panel: Impact of Pathogenic Variants in Other Genes beyondBRCA1/2