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
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引用次数: 2
摘要
背景/目的：种系拷贝数变异（CNV）是一种易患遗传性癌症的遗传变异。如今，下一代测序（NGS）技术已经为临床实践中的多基因面板分析做出了贡献。材料和方法：采用基于溶液的捕获方法对2163例癌症患者进行易感性筛查。一组52个基因用于靶向NGS。基于捕获的方法能够从NGS数据中对CNV进行计算分析。我们研究了商业软件套件SeqPilot（JSI Medical Systems）的CNV模块和非商业工具panelcn的性能。拖把。此外，我们还测试了数字多重连接依赖性探针扩增（digitalMLPA）的性能。结果：在464个样本中（21.5%）发现了致病性/可能致病性变异（P/LP）。CNV占致病性变异的10.8%（50/464），指的是一个基因的一个或多个外显子的缺失/重复。在癌症和卵巢癌患者中，CNVs分别占10.2%和6.8%的致病性变异。在结直肠癌癌症患者中，CNV占致病性/可能致病性变体的28.6%。结论：计算机CNV检测工具为从NGS实验中识别CNV提供了一种可行且经济高效的方法。CNVs在P/LP变体中占很大比例，因为它们代表了NGS多基因分析确定的每十个P/LP发现中的一个；因此，强烈建议对其进行评价，以提高遗传性癌症分析的诊断率。
Copy Number Variations (CNVs) Account for 10.8% of Pathogenic Variants in Patients Referred for Hereditary Cancer Testing.
Background/aim: 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.
Materials and methods: 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).
Results: 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.
Conclusion: 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.
期刊介绍：
Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004.
Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal.
Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.
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