复制数变异(CNVs)占患者转诊进行遗传性癌症检测的致病变异的10.8%。
Copy Number Variations (CNVs) Account for 10.8% of Pathogenic Variants in Patients Referred for Hereditary Cancer Testing.
发表日期：2023
作者：
Konstantinos Agiannitopoulos, Georgia Pepe, Georgios N Tsaousis, Kevisa Potska, Dimitra Bouzarelou, Anastasia Katseli, Christina Ntogka, Angeliki Meintani, Nikolaos Tsoulos, Stylianos Giassas, Vassileios Venizelos, Christos Markopoulos, Rodoniki Iosifidou, Sofia Karageorgopoulou, Christos Christodoulou, Ioannis Natsiopoulos, Konstantinos Papazisis, Maria Vasilaki-Antonatou, Eleftherios Kabletsas, Amanta Psyrri, Dimitrios Ziogas, Efthalia Lalla, Anna Koumarianou, Kornilia Anastasakou, Christos Papadimitriou, Vahit Ozmen, Sualp Tansan, Kerim Kaban, Tahsin Ozatli, Dan Tudor Eniu, Angelica Chiorean, Alexandru Blidaru, Marrit Rinsma, Eirini Papadopoulou, George Nasioulas
来源：
GENOMICS PROTEOMICS & BIOINFORMATICS
摘要：
生殖细胞拷贝数变异（CNV）是一种导致遗传性癌症显著易感的遗传变异类型。如今，下一代测序（NGS）技术在临床实践中对多基因面板分析做出了贡献。总计2,163名患者通过基于溶液的捕获方法进行了癌症易感性筛查。使用一套包含52个基因的面板进行有针对性的NGS。基于捕获的方法使得从NGS数据中计算分析CNV成为可能。我们研究了商业软件套件SeqPilot（JSI Medical Systems）和非商业工具panelcn.MOPS的CNV模块的性能。此外，我们还测试了数字多重连接依赖探针扩增（digitalMLPA）的性能。
致病/可能致病变异（P/LP）被鉴定在464个样本中（21.5%）。CNV占据了致病变异的10.8%（50/464），指的是一个或多个基因外显子的缺失/复制。在乳腺癌和卵巢癌患者中，CNV分别占致病变异的10.2%和6.8%。在结直肠癌患者中，CNV占据了28.6%的致病/可能致病变异。
体外CNV检测工具提供了一种可行且经济高效的方法，可以从NGS实验中识别CNV。CNV构成了P/LP变异的相当比例，因为它们代表了通过NGS多基因分析鉴定出的每十个P/LP结果中的一个；因此，高度推荐对它们进行评估，以提高遗传性癌症分析的诊断效果。
版权所有 © 2023，国际抗癌研究学会（George J. Delinasios医生），保留所有权利。
Germline copy number variation (CNV) is a type of genetic variant that predisposes significantly to inherited cancers. Today, next-generation sequencing (NGS) technologies have contributed to multi gene panel analysis in clinical practice.A total of 2,163 patients were screened for cancer susceptibility, using a solution-based capture method. A panel of 52 genes was used for targeted NGS. The capture-based approach enables computational analysis of CNVs from NGS data. We studied the performance of the CNV module of the commercial software suite SeqPilot (JSI Medical Systems) and of the non-commercial tool panelcn.MOPS. Additionally, we tested the performance of digital multiplex ligation-dependent probe amplification (digitalMLPA).Pathogenic/likely pathogenic variants (P/LP) were identified in 464 samples (21.5%). CNV accounts for 10.8% (50/464) of pathogenic variants, referring to deletion/duplication of one or more exons of a gene. In patients with breast and ovarian cancer, CNVs accounted for 10.2% and 6.8% of pathogenic variants, respectively. In colorectal cancer patients, CNV accounted for 28.6% of pathogenic/likely pathogenic variants.In silico CNV detection tools provide a viable and cost-effective method to identify CNVs from NGS experiments. CNVs constitute a substantial percentage of P/LP variants, since they represent up to one of every ten P/LP findings identified by NGS multigene analysis; therefore, their evaluation is highly recommended to improve the diagnostic yield of hereditary cancer analysis.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.