使用新一代测序（NGS）和荧光原位杂交（FISH）检测中国患者的 MET 扩增的综合数据有限，我们使用 FISH 作为参考来评估组织和血浆样本中的 NGS 性能。我们还试图通过生物信息学方法找到 NGS 检测 MET 扩增的最佳阈值。患者在入组第一代、第二代或第三代 (G) EGFR-TKI 后病情出现进展。通过 NGS 和 FISH 对组织活检样本进行 MET 扩增检测。收集配对血浆样本，通过 NGS 进行 MET 扩增检测。分析了 NGS 和 FISH 之间的敏感性、特异性和一致性。对 116 名符合条件的患者进行了分析。 44名患者为男性。 82 名患者接受了第三代 EGFR-TKI 治疗。 FISH 在 43 例 (37.1%) 患者中检测到 MET 扩增，其中 19 例 (16.4%) 多体性和 24 例 (20.7%) 局灶性扩增。第3代EGFR-TKI后和第1/2代EGFR-TKI耐药患者MET扩增阳性率分别为42.7%（35/82）和23.5%（8/34）。通过 NGS 检测组织中 MET 扩增的灵敏度、特异性和一致性分别为 39.5% (17/43)、98.6% (72/73) 和 76.7% (89/116)、66.7% (16/24)、98.6组织中局部 MET 扩增分别为 % (72/73) 和 90.7% (88/97)，血浆中局部扩增分别为 29.2% (7/24)、94.5% (69/73)、78.4% (76/97)。结果如下表所示。NGS 是组织中 MET 局灶扩增检测的替代方法。虽然血浆 NGS 检测的灵敏度需要进一步提高，以最大限度地识别可能从双靶向治疗中获益的患者。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Comprehensive data using Next-Generation Sequence (NGS) and fluorescence in situ hybridization (FISH) for detecting MET amplification is limited in Chinese patients, we evaluating NGS performance both in tissue and plasma samples using FISH as reference. We also sought to find optimal thresholds value for NGS in detecting MET amplification via bioinformatics methods.Patients progressed after 1st-, 2nd-, or 3rd-generation (G) EGFR-TKIs were enrolled. Tissue biopsy samples were performed for MET amplification detection via both NGS and FISH. Paired plasma samples were collected for MET amplification detection by NGS. The sensitivity, specificity and agreement were analyzed between NGS and FISH.116 eligible patients were analyzed. 44 patients were male. 82 patients were after 3rd generation EGFR-TKI. MET amplification was detected in 43 (37.1 %) patients by FISH, including 19 (16.4 %) polysomy and 24 (20.7 %) focal amplification. The positive rate of MET amplification in post 3rd generation EGFR-TKI and post 1st/2ndgeneration EGFR-TKI resistant patients was 42.7 % (35/82), and 23.5 % (8/34). The sensitivity, specificity and agreement of detecting MET amplification by NGS in tissue were 39.5 % (17/43), 98.6 % (72/73) and 76.7 % (89/116), respectively, 66.7 % (16/24), 98.6 % (72/73) and 90.7 % (88/97) for focal MET amplification in tissue and 29.2 % (7/24), 94.5 % (69/73), 78.4 % (76/97) for focal amplification in plasma. Results were shown in the table below.NGS is an alternative method for MET focal amplification detection in tissue. While the sensitivity of NGS testing in plasma needs further improvement to maximize identification of patients with potential benefit from dual-targeted therapy.Copyright © 2024 Elsevier B.V. All rights reserved.