遗传性癌症的临床和遗传概况：来自单一临床诊断实验室的经验。
The Clinical and Genetic Landscape of Hereditary Cancer: Experience from a Single Clinical Diagnostic Laboratory.
发表日期：2024
作者：
Nikolaos Tsoulos, Konstantinos Agiannitopoulos, Kevisa Potska, Anastasia Katseli, Christina Ntogka, Georgia Pepe, Dimitra Bouzarelou, Athanasios Papathanasiou, Dimitrios Grigoriadis, Georgios N Tsaousis, Helen Gogas, Theodore Troupis, Konstantinos Papazisis, Ioannis Natsiopoulos, Vassileios Venizelos, Kyriakos Amarantidis, Stylianos Giassas, Christos Papadimitriou, Elena Fountzilas, Maroulio Stathoulopoulou, Anna Koumarianou, Grigorios Xepapadakis, Alexandru Blidaru, Daniela Zob, Oana Voinea, Mustafa Özdoğan, Mahmut Çerkez Ergören, Alinta Hegmane, Eirini Papadopoulou, George Nasioulas, Christos Markopoulos
来源：
GENOMICS PROTEOMICS & BIOINFORMATICS
摘要：
新一代测序（NGS）技术在遗传性癌症基因研究中的应用对于临床监测、治疗方法和降低发生新恶性肿瘤的风险具有重要意义。该研究的目的是探索被转诊为遗传性癌症的个体的遗传易感性。2020-2023 年期间，共有 8,261 名个体被转诊在实验室进行多基因基因检测，并使用 NGS 进行了多基因基因检测。在接受检查的个体中，56.17%被诊断为乳腺癌，6.77%被诊断为卵巢癌，2.88%被诊断为结直肠癌，1.91%被诊断为前列腺癌，6.43%是健康的，有明显的癌症家族史，而3.06%是其他类型的癌症癌症的 0.21% 没有提供任何信息。此外，我们对 85 名患有乳腺癌的女性进行了全外显子组测序分析。20% 的受检个体携带致病性变异。具体而言，54.8% 的患者在临床上显着的基因（BRCA1、BRCA2、PALB2、RAD51C、PMS2、CDKN2A、MLH1、MSH2、TP53、MSH6、APC、RAD51D、PTEN、RET、CDH1、MEN1 和VHL）。在检测到的不同类型的致病变异中，很大一部分（6.52%）代表拷贝数变异（CNV）。通过WES分析，检测到以下结果： CTC1：c.880C>T，p.(Gln294*)； MLH3: c.405del, p.(Asp136Metfs*2)、PPM1D: c.1426_1430del, p.(Glu476Leufs*3) 和 SDHB: c.395A>G, p.(His132Arg)。对致病变异携带者进行适当的临床管理。此外，获得的信息对于确定受检查个体的家庭成员患恶性肿瘤的风险非常重要。版权所有 © 2024，国际抗癌研究所（George J. Delinasios 博士），保留所有权利。
The application of next-generation sequencing (NGS) technology in the genetic investigation of hereditary cancer is important for clinical surveillance, therapeutic approach, and reducing the risk of developing new malignancies. The aim of the study was to explore genetic predisposition in individuals referred for hereditary cancer.A total of 8,261 individuals were referred for multigene genetic testing, during the period 2020-2023, in the laboratory, and underwent multigene genetic testing using NGS. Among the examined individuals, 56.17% were diagnosed with breast cancer, 6.77% with ovarian cancer, 2.88% with colorectal cancer, 1.91% with prostate cancer, 6.43% were healthy with a significant family history of cancer, while 3.06% had a different type of cancer and 0.21% had not provided any information. Additionally, in 85 women with breast cancer we performed whole exome sequencing analysis.20% of the examined individuals carried a pathogenic variant. Specifically, 54.8% of the patients had a pathogenic variant in a clinically significant gene (BRCA1, BRCA2, PALB2, RAD51C, PMS2, CDKN2A, MLH1, MSH2, TP53, MSH6, APC, RAD51D, PTEN, RET, CDH1, MEN1, and VHL). Among the different types of pathogenic variants detected, a significant percentage (6.52%) represented copy number variation (CNV). With WES analysis, the following findings were detected: CTC1: c.880C>T, p.(Gln294*); MLH3: c.405del, p.(Asp136Metfs*2), PPM1D: c.1426_1430del, p.(Glu476Leufs*3), and SDHB: c.395A>G, p.(His132Arg).Comprehensive multigene genetic testing is necessary for appropriate clinical management of pathogenic variants' carriers. Additionally, the information obtained is important for determining the risk of malignancy development in family members of the examined individuals.Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.