Genekor Medical S.A, Athens, Greece;
Genekor Medical S.A, Athens, Greece.
Cancer Genomics Proteomics. 2021 May-Jun;18(3):285-294. doi: 10.21873/cgp.20259.
Classification of splicing variants (SVs) in genes associated with hereditary cancer is often challenging. The aim of this study was to investigate the occurrence of SVs in hereditary cancer genes and the clinical utility of RNA analysis.
1518 individuals were tested for cancer predisposition, using a Next Generation Sequencing (NGS) panel of 36 genes. Splicing variant analysis was performed using RT-PCR and Sanger Sequencing.
In total, 34 different SVs were identified, 53% of which were classified as pathogenic or likely pathogenic. The remaining 16 variants were initially classified as Variant of Uncertain Significance (VUS). RNA analysis was performed for 3 novel variants.
The RNA analysis assisted in the reclassification of 20% of splicing variants from VUS to pathogenic. RNA analysis is essential in the case of uncharacterized splicing variants, for proper classification and personalized management of these patients.
与遗传性癌症相关基因的剪接变异（SV）分类通常具有挑战性。本研究旨在调查遗传性癌症基因中 SV 的发生情况以及 RNA 分析的临床效用。
使用针对 36 个基因的下一代测序 (NGS) 面板，对 1518 个人进行癌症易感性检测。使用 RT-PCR 和 Sanger 测序进行剪接变异分析。
总共鉴定出 34 种不同的 SV，其中 53%被归类为致病性或可能致病性。其余 16 个变体最初被归类为意义不确定的变异 (VUS)。对 3 个新变体进行了 RNA 分析。
RNA 分析有助于将 20%的剪接变异从 VUS 重新分类为致病性。在未表征的剪接变异的情况下，RNA 分析对于正确分类和对这些患者进行个性化管理至关重要。
