Meintani Angeliki, Ozdogan Mustafa, Touroutoglou Nikolaos, Papazisis Konstantinos, Boukovinas Ioannis, Bilir Cemil, Giassas Stylianos, Sualp Tansan, Lacin Sahin, Dan Corneliu Jinga, Kosmidis Paraskevas, Ozatli Tahsin, Ziogas Dimitrios, Theochari Maria, Botsolis Konstantinos, Kapetsis George, Tsantikidi Aikaterini, Florou-Chatzigiannidou Chrysiida, Maxouri Styliani, Metaxa-Mariatou Vasiliki, Grigoriadis Dimitrios, Papathanasiou Athanasios, Tsaousis Georgios N, Kollia Panagoula, Trougakos Ioannis, Agathangelidis Andreas, Papadopoulou Eirini, Nasioulas George
Genekor Medical S.A., 15344 Athens, Greece.
Division of Medical Oncology, Memorial Antalya Hospital, Antalya 07025, Türkiye.
Int J Mol Sci. 2025 Jun 20;26(13):5930. doi: 10.3390/ijms26135930.
In the era of precision oncology, comprehensive molecular profiling is critical for guiding targeted and immunotherapy strategies. This study presents the analytical and clinical validation of a 1021-gene next-generation sequencing (NGS) panel, designed for use with both formalin-fixed paraffin-embedded (FFPE) tissue- and liquid-biopsy specimens. Analytical validation confirmed the assay's high sensitivity and specificity across variant types-including SNVs (Single Nucleotide Variations), indels, CNVs (Copy Number Variations), and fusions-down to a 0.5% variant allele frequency. The assay also accurately identified microsatellite instability (MSI) and tumor mutational burden (TMB), essential biomarkers for immunotherapy. Clinical validation was performed on over 1300 solid tumor samples from diverse histologies, revealing actionable alterations in over 50% of cases. The panel detected on-label treatment biomarkers in 12.57% of patients, increasing to 20.15% when immunotherapy markers were included. Additionally, the assay demonstrated strong concordance with orthogonal methods and was effective in detecting variants in plasma-derived circulating tumor DNA in 70% of evaluable cases. These findings support the robust performance and broad clinical applicability of the 1021-gene panel for comprehensive genomic profiling in both tissue and liquid biopsies, offering a valuable tool for personalized cancer treatment.
在精准肿瘤学时代，全面的分子谱分析对于指导靶向治疗和免疫治疗策略至关重要。本研究展示了一个1021基因的二代测序（NGS）检测板的分析和临床验证，该检测板设计用于福尔马林固定石蜡包埋（FFPE）组织样本和液体活检样本。分析验证证实了该检测方法在各种变异类型（包括单核苷酸变异（SNV）、插入缺失、拷贝数变异（CNV）和融合）中的高灵敏度和特异性，低至0.5%的变异等位基因频率。该检测方法还能准确识别微卫星不稳定性（MSI）和肿瘤突变负荷（TMB），这是免疫治疗的重要生物标志物。对来自不同组织学类型的1300多个实体瘤样本进行了临床验证，结果显示超过50%的病例存在可采取行动的改变。该检测板在12.57%的患者中检测到标签上的治疗生物标志物，若纳入免疫治疗标志物，这一比例增至20.15%。此外，该检测方法与正交方法显示出高度一致性，在70%的可评估病例中能有效检测血浆来源的循环肿瘤DNA中的变异。这些发现支持了该1021基因检测板在组织活检和液体活检中进行全面基因组分析时的强大性能和广泛临床适用性，为个性化癌症治疗提供了一个有价值的工具。
