Genomic Laboratory (GLAB), Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
Department of Medical Genetics, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
Expert Rev Mol Diagn. 2022 Feb;22(2):239-246. doi: 10.1080/14737159.2022.2048373. Epub 2022 Mar 10.
Copy number variations (CNVs) are commonly associated with malignancies, including hereditary breast and ovarian cancers. Next generation sequencing (NGS) provides solutions for CNV detection in a single run. This study aimed to compare the accuracy of CNV detection by NGS analyzing tool against Multiplex Ligation Dependent Probe Amplification (MLPA).
In total, 1276 cases were studied by targeted NGS panels and 691 cases (61 calls in 58 NGS-CNV positive and 633 NGS-CNV negative cases) were validated by MLPA.
Twenty-eight (46%) NGS-CNV positive calls were consistent, whereas 33 (54%) calls showed discordance with MLPA. Two cases were detected as SNV by the NGS and CNV by the MLPA analysis. In total, 2% of the cases showed an MLPA confirmed CNV region in . The results of this study showed that despite the high false positive call rate of the NGS-CNV algorithm, there were no false negative calls. The cases that were determined to be negative by the NGS and positive by the MLPA were actually carrying SNVs that were located on the MLPA probe binding sites.
The diagnostic performance of NGS-CNV analysis is promising; however, the need for confirmation by different methods remains.
拷贝数变异（CNV）通常与恶性肿瘤有关，包括遗传性乳腺癌和卵巢癌。下一代测序（NGS）为单次运行中的 CNV 检测提供了解决方案。本研究旨在比较 NGS 分析工具与多重连接依赖性探针扩增（MLPA）检测 CNV 的准确性。
共对 1276 例进行了靶向 NGS 面板分析，对 691 例（61 个在 58 例 NGS-CNV 阳性和 633 例 NGS-CNV 阴性病例中存在的阳性 CNV ）进行了 MLPA 验证。
28 个（46%）NGS-CNV 阳性 CNV 检测结果一致，33 个（54%）检测结果不一致。2 例被 NGS 检测为 SNV，而被 MLPA 分析检测为 CNV。共有 2%的病例在. 中显示出 MLPA 确认的 CNV 区域。本研究结果表明，尽管 NGS-CNV 算法的假阳性率较高，但没有假阴性。被 NGS 判定为阴性而被 MLPA 判定为阳性的病例实际上携带了位于 MLPA 探针结合位点的 SNV。
NGS-CNV 分析的诊断性能很有前景，但仍需要通过不同的方法进行确认。
