表皮生长因子受体(EGFR)外显子20插入突变(E20ins)是非小细胞肺癌中观察到的第三常见突变,约占所有EGFR突变的1-10%。在精准医学和靶向治疗的时代,遗传改变的一致命名对于避免混淆和错误至关重要。然而,EGFRE20ins突变的注释一直不一致,导致科学文献和产品文档的混乱。在这项研究中,我们的主要目的是调查独立研究中EGFRE20蛋白相关不同注释的使用情况.此外,我们评估了EGFRE20ins突变的分布,并估计了每个可用的EGFRE20ins检测试验的预期检测覆盖率.从六项研究中收集了总共1,418个EGFRE20ins突变(FoundationInsights,GeneseeqTechnologyInc.莫博替尼I/II期试验,波齐替尼II期试验,sunvozertinibI期试验,和三星医学中心),并根据人类基因组变异协会(HGVS)命名法进行了重组。我们的分析显示,大多数需要校正的EGFRE20ins突变是“插入”或“缺失-插入”,应适当指定为\'重复\'。此外,在每项研究中使用不同的注释报告了重复的变体,而且,即使相同的变体序列在同一研究中也被不同地注释。在所有六项研究中,p.A767_V769dup和p.S768_D770dup是最常见的EGFRE20蛋白。OncomineDx目标测试显示患者覆盖率最高,为77.2%,其次是DroplexEGFR突变测试v2,EGFRE20ins患者的患者覆盖率为70.5%。为了确保在现实世界中全面覆盖,必须标准化每个变体的注释,例如使用HGVS命名法。EGFRE20中药物反应性的准确分类和分析需要考虑命名法,特别是关于实际突变发生的位置。
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (E20ins) are the third most frequent mutations observed in non-small cell lung cancer, accounting for approximately 1-10% of all EGFR mutations. In the era of precision medicine and targeted therapies, consistent naming of genetic alterations is crucial to avoid confusion and errors. However, the annotation of EGFR E20ins mutations has been inconsistent, leading to confusion in the scientific literature and product documentation. In this study, our primary objective was to investigate the usage of different annotation related to EGFR E20ins in independent studies. Additionally, we assessed the distribution of EGFR E20ins mutations and estimated the detection coverage expected from each available EGFR E20ins detection assay. A total of 1,418 EGFR E20ins mutations were collected from six studies (FoundationInsights, Geneseeq Technology Inc, mobocertinib phase I/II trial, poziotinib phase II trial, sunvozertinib phase I trial, and Samsung Medical Center) and reorganised according to Human Genome Variation Society (HGVS) nomenclature. Our analysis revealed that the majority of EGFR E20ins mutations requiring correction were \'insertion\' or \'deletion-insertion\', which should be appropriately designated as \'duplication\'. Additionally, duplicated variants were reported using different annotations in each study, and furthermore, even identical variant sequences were annotated differently within the same study. In all six studies, p.A767_V769dup and p.S768_D770dup were the most frequently observed EGFR E20ins. The Oncomine Dx Target Test showed the highest patient coverage at 77.2%, followed by the Droplex EGFR Mutation Test v2 with a patient coverage of 70.5% for EGFR E20ins patients. To ensure comprehensive coverage in real-world settings, it is essential to standardise the annotations for each variant, for example using the HGVS nomenclature. The accurate classification and analysis of drug responsiveness in EGFR E20ins necessitate consideration of the nomenclature, particularly with respect to the locations where the actual mutations occur.