Abstract：
Big data generated from exome sequencing (ES) and genome sequencing (GS) analyses can be used to detect actionable and high-penetrance variants that are not directly associated with the primary diagnosis of patients but can guide their clinical follow-up and treatment. Variants that are classified as pathogenic/likely pathogenic and are clinically significant but not directly associated with the primary diagnosis of patients are defined as secondary findings (SF). The aim of this study was to examine the frequency and variant spectrum of cancer-related SF in 2020 Turkish ES data and to discuss the importance of the presence of cancer-related SF in at-risk family members in terms of genetic counseling and follow-up. A total of 2020 patients from 2020 different families were evaluated by ES. SF were detected in 28 unrelated cases (1.38%), and variants in BRCA2 (11 patients) and MLH1 (4 patients) genes were observed most frequently. A total of 21 different variants were identified, with 4 of them (c.9919_9932del and c.3653del in the BRCA2 gene, c.2002A>G in the MSH2 gene, c.26_29del in the TMEM127 gene) being novel variations. In three different families, c.1189C>T (p.Gln397*) variation in BRCA2 gene was detected, suggesting that this may be a common variant in the Turkish population. This study represents the largest cohort conducted in the Turkish population, examining the frequency and variant spectrum of cancer-related SF. With the identification of frequent variations and the detection of novel variations, the findings of this study have contributed to the variant spectrum. Genetic testing conducted in family members is presented as real-life data, showcasing the implications in terms of counseling, monitoring, and treatment through case examples.
摘要：
外显子组测序（ES）和基因组测序（GS）分析产生的大数据可用于检测可操作和高外显率变异，这些变异与患者的初步诊断没有直接关系，但可以指导他们的临床随访和治疗。被分类为致病性/可能致病性并且具有临床意义但与患者的主要诊断不直接相关的变体被定义为次要发现(SF)。这项研究的目的是检查2020年土耳其ES数据中与癌症相关的SF的频率和变异谱，并讨论在遗传咨询和随访方面，有风险的家庭成员中与癌症相关的SF的存在的重要性。ES对来自2020个不同家庭的2020名患者进行了评估。在28例无关病例中检测到SF（1.38％），BRCA2(11例患者)和MLH1(4例患者)基因变异最常见。总共鉴定了21种不同的变体，其中4个（BRCA2基因中c.9919_9932del和c.3653del，c.2002A>MSH2基因中的G，TMEM127基因中的c.26_29del）是新的变异。在三个不同的家庭，c.1189C>T（p。检测到BRCA2基因中的Gln397*）变异，这表明这可能是土耳其人口中的常见变体。这项研究代表了在土耳其人口中进行的最大的队列，检查癌症相关SF的频率和变异谱。随着频繁变化的识别和新变化的检测，这项研究的发现促成了变异谱。在家庭成员中进行的基因检测是作为真实数据呈现的，展示了咨询方面的影响，监测,并通过案例进行治疗。
