Institute of Pathology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 62, 50924, Cologne, Germany.
Institute of Pathology, University Hospital Erlangen, Krankenhausstr. 8-10, 91054, Erlangen, Germany.
Sci Rep. 2024 Jun 6;14(1):13069. doi: 10.1038/s41598-024-63821-2.
Insertion mutations in exon 20 of the epidermal growth factor receptor gene (EGFR exon20ins) are rare, heterogeneous alterations observed in non-small cell lung cancer (NSCLC). With a few exceptions, they are associated with primary resistance to established EGFR tyrosine kinase inhibitors (TKIs). As patients carrying EGFR exon20ins may be eligible for treatment with novel therapeutics-the bispecific antibody amivantamab, the TKI mobocertinib, or potential future innovations-they need to be identified reliably in clinical practice for which quality-based routine genetic testing is crucial. Spearheaded by the German Quality Assurance Initiative Pathology two international proficiency tests were run, assessing the performance of 104 participating institutes detecting EGFR exon20ins in tissue and/or plasma samples. EGFR exon20ins were most reliably identified using next-generation sequencing (NGS). Interestingly, success rates of institutes using commercially available mutation-/allele-specific quantitative (q)PCR were below 30% for tissue samples and 0% for plasma samples. Most of these mutation-/allele-specific (q)PCR assays are not designed to detect the whole spectrum of EGFR exon20ins mutations leading to false negative results. These data suggest that NGS is a suitable method to detect EGFR exon20ins in various types of patient samples and is superior to the detection spectrum of commercially available assays.
表皮生长因子受体基因（EGFR 外显子 20 插入）的插入突变是一种罕见的非小细胞肺癌（NSCLC）中观察到的异质性改变。除了少数例外，它们与已建立的 EGFR 酪氨酸激酶抑制剂（TKI）的原发性耐药有关。由于携带 EGFR 外显子 20 插入的患者可能有资格接受新型治疗药物——双特异性抗体 amivantamab、TKI mobocertinib 或未来可能的创新药物治疗——因此需要在临床实践中可靠地识别，这对于基于质量的常规基因检测至关重要。由德国质量保证倡议病理学牵头，进行了两次国际能力验证测试，评估了 104 个参与机构在组织和/或血浆样本中检测 EGFR 外显子 20 插入的性能。使用下一代测序（NGS）最可靠地鉴定了 EGFR 外显子 20 插入。有趣的是，使用市售的突变/等位基因特异性定量（q）PCR 的机构的成功率在组织样本中低于 30%，在血浆样本中为 0%。这些突变/等位基因特异性（q）PCR 检测大多数都不是为了检测 EGFR 外显子 20 插入的整个突变谱而设计的，因此会导致假阴性结果。这些数据表明，NGS 是一种在各种类型的患者样本中检测 EGFR 外显子 20 插入的合适方法，优于市售检测方法的检测范围。
