文章：

在高度异质性患者队列中遗传性癌症综合征的新型致病性变异：多基因分析的启示

Novel Pathogenic Variants in Hereditary Cancer Syndromes in a Highly Heterogeneous Cohort of Patients: Insights from Multigene Analysis

原文发布日期：23 December 2023

DOI: 10.3390/cancers16010085

类型: Article

开放获取: 是

英文摘要：

Cancer is a major global public health challenge, affecting both quality of life and mortality. Recent advances in genetic research have uncovered hereditary cancer syndromes (HCS) that predispose individuals to malignant neoplasms. While traditional single-gene testing has focused on high-penetrance genes, the past decade has seen a shift toward multigene panels, which facilitate the analysis of multiple genes associated with specific HCS. This approach reveals variants in less-studied gene regions and improves our understanding of cancer predisposition. In a study composed of Russian patients with clinical signs of HCS, we used a multigene hereditary cancer panel and revealed 21.6% individuals with pathogenic or likely pathogenic genetic variants.BRCA1/BRCA2mutations predominated, followed by theCHEK2andATMvariants. Of note, 16 previously undescribed variants were identified in theMUTYH,GALNT12,MSH2,MLH1,MLH3,EPCAM, andPOLEgenes. The implications of the study extend to personalized cancer prevention and treatment strategies, especially in populations lacking extensive epidemiological data, such as Russia. Overall, our research provides valuable genetic insights that give the way for further investigation and advances in the understanding and management of hereditary cancer syndromes.

摘要翻译： 

癌症是全球公共卫生领域的一项重大挑战，深刻影响着人类的生活质量与生存率。近年来遗传学研究进展揭示了遗传性癌症综合征的存在，这类综合征显著增加了个体罹患恶性肿瘤的风险。传统单基因检测主要聚焦于高外显率基因，而过去十年间，多基因检测技术逐渐兴起，该技术能同步分析与特定遗传性癌症综合征相关的多个基因。这种方法不仅揭示了研究较少的基因区域变异，还深化了我们对癌症遗传易感机制的理解。在一项针对具有遗传性癌症综合征临床特征的俄罗斯患者研究中，我们采用多基因遗传性癌症检测技术，发现21.6%的个体携带致病性或疑似致病性基因变异。其中BRCA1/BRCA2基因突变最为常见，其次为CHEK2和ATM基因变异。值得注意的是，我们在MUTYH、GALNT12、MSH2、MLH1、MLH3、EPCAM及POLE基因中发现了16个既往未报道的新变异。本研究对个性化癌症防治策略的制定具有重要启示，尤其对俄罗斯这类缺乏系统流行病学数据的地区更具参考价值。总体而言，我们的研究提供了宝贵的遗传学见解，为深入探索遗传性癌症综合征的机制及临床管理奠定了重要基础。

原文链接：

Novel Pathogenic Variants in Hereditary Cancer Syndromes in a Highly Heterogeneous Cohort of Patients: Insights from Multigene Analysis