Detection of MET amplification by droplet digital PCR in peripheral blood samples of non-small cell lung cancer

Fan, Ying; Sun, Rui; Wang, Zhizhong; Zhang, Yuying; Xiao, Xiao; Liu, Yizhe; Xin, Beibei; Xiong, Hui; Lu, Daru; Ma, Jie

doi:10.1007/s00432-022-04048-4

Cited by 15 publications

(13 citation statements)

References 60 publications

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“…Furthermore, the literature suggests that, compared with other assays, FISH is unique in that it can capture the various levels of MET gene amplification, including "true" highlevel MET gene amplified cases characterized by a high MET GCN (≥6 per cell) without concomitant polysomy (i.e., a high MET/CEN7 ratio) [64]. However, FISH only detects tissue samples, and it is inapplicable when tissue samples are not available, which limits its clinical use [65].…”

Section: Fluorescence In Situ Hybridization (Fish)mentioning

confidence: 99%

“…Although seldomly used, the detection of MET amplification using ddPCR shows very high concordance rates with FISH, either in tissue samples only (100%, 102/102) or among both peripheral blood and tissue samples (94.17%, 97/103). This indicates that ddPCR is an optional non-invasive method for detecting of MET CNG in blood samples as compared with the FISH method in tissue samples; thus, it may be an alternative method for MET amplification detection when FISH is not applicable, especially when tumor tissue is not available [65]. Again, cut-off values vary, and consensus on the standard definition for MET amplification by PCR remains to be proposed.…”

Section: Reverse-transcription Polymerase Chain Reaction-qrt-pcrmentioning

confidence: 99%

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MET Amplification as a Resistance Driver to TKI Therapies in Lung Cancer: Clinical Challenges and Opportunities

Qin

Hong

Zhang

et al. 2023

Cancers

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Targeted therapy has emerged as an important pillar for the standard of care in oncogene-driven non-small cell lung cancer (NSCLC), which significantly improved outcomes of patients whose tumors harbor oncogenic driver mutations. However, tumors eventually develop resistance to targeted drugs, and mechanisms of resistance can be diverse. MET amplification has been proven to be a driver of resistance to tyrosine kinase inhibitor (TKI)-treated advanced NSCLC with its activation of EGFR, ALK, RET, and ROS-1 alterations. The combined therapy of MET-TKIs and EGFR-TKIs has shown outstanding clinical efficacy in EGFR-mutated NSCLC with secondary MET amplification-mediated resistance in a series of clinical trials. In this review, we aimed to clarify the underlying mechanisms of MET amplification-mediated resistance to tyrosine kinase inhibitors, discuss the ways and challenges in the detection and diagnosis of MET amplifications in patients with metastatic NSCLC, and summarize the recently published clinical data as well as ongoing trials of new combination strategies to overcome MET amplification-mediated TKI resistance.

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Section: Fluorescence In Situ Hybridization (Fish)mentioning

confidence: 99%

Section: Reverse-transcription Polymerase Chain Reaction-qrt-pcrmentioning

confidence: 99%

MET Amplification as a Resistance Driver to TKI Therapies in Lung Cancer: Clinical Challenges and Opportunities

Qin

Hong

Zhang

et al. 2023

Cancers

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“…Numerous studies have been conducted to validate the potential of non-invasive strategies for identifying the resistance mechanisms to EGFR-TKIs. Table 2 lists recent literature data on gene alterations in plasma during EGFR-TKI therapy [ 45 , 47 , 52 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. More than half of patients with EGFR mutations develop EGFR T790M resistance when using first- and second-generation EGFR-TKIs [ 110 ].…”

Section: Evaluation Of Resistance To Egfr-tki Therapy Based On Plasma...mentioning

confidence: 99%

“…The second most common resistance mechanism was MET amplification. Patients who were resistant to third-generation EGFR-TKIs have been found to have significantly increased rates of MET amplification [ 109 ], occurring in approximately 15% of cases, compared to patients who were resistant to first- and second-generation EGFR-TKIs [ 118 ]. Moreover, the patterns of genomic alterations in patients with innate and acquired resistance to osimertinib were significantly different.…”

Section: Evaluation Of Resistance To Egfr-tki Therapy Based On Plasma...mentioning

confidence: 99%

Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?

Kong

Liu

et al. 2023

JCM

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More and more clinical trials have explored the role of liquid biopsy in the diagnosis and treatment of EGFR-mutated NSCLC. In certain circumstances, liquid biopsy has unique advantages and offers a new way to detect therapeutic targets, analyze drug resistance mechanisms in advanced patients, and monitor MRD in patients with operable NSCLC. Although its potential cannot be ignored, more evidence is needed to support the transition from the research stage to clinical application. We reviewed the latest progress in research on the efficacy and resistance mechanisms of targeted therapy for advanced NSCLC patients with plasma ctDNA EGFR mutation and the evaluation of MRD based on ctDNA detection in perioperative and follow-up monitoring.

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“…Moreover, Ying Fan et al found that MET amplification detection via tissue ddPCR aligned closely with FISH results (102/102, 100%), which highlighted the potential of ddPCR as an alternative method for MET amplification detection. 21 However, the direct comparison of tissue FISH and paired plasma ddPCR for MET amplification testing, as well as the clinical utility of ddPCR for MET amplification detection in NSCLC, have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Plasma ddPCR for the detection of MET amplification in advanced NSCLC patients: a comparative real-world study

Su,

Weng,

Lin

et al. 2024

Ther Adv Med Oncol

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Background: Mesenchymal–epithelial transition ( MET) amplification is a crucial oncogenic driver and a resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) of non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection. However, it is inapplicable when tissue samples are unavailable. Objective: This study assessed the performance of plasma droplet digital polymerase chain reaction (ddPCR) in MET amplification detection in NSCLC patients. Design and methods: A total of 87 NSCLC patients were enrolled, and 94 paired tissue and plasma samples were analyzed for the concordance between FISH and plasma ddPCR/tissue next-generation sequencing (NGS) in detecting MET amplification. In addition, the efficacy of patients with MET amplification using different detection methods who were treated with MET-TKIs was evaluated. Results: Plasma ddPCR showed substantial concordance with FISH (74.1% sensitivity, 92.5% specificity, and 87.2% accuracy with a kappa value of 0.68) and outperformed tissue NGS (kappa value of 0.64) in MET amplification detection. Combined plasma ddPCR and tissue NGS showed substantial concordance with FISH (92.3% sensitivity, 89.2% specificity, and an accuracy of 90.1% with a kappa value of 0.77). The efficacy is comparable in these NSCLC patients with MET amplification detected by FISH and plasma ddPCR who were treated with MET-TKIs. Conclusion: Plasma ddPCR is a potentially reliable method for detecting MET amplification in advanced NSCLC patients. Combined plasma ddPCR and tissue NGS might be an alternative or complementary method to MET amplification detection.

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Detection of MET amplification by droplet digital PCR in peripheral blood samples of non-small cell lung cancer

Cited by 15 publications

References 60 publications

MET Amplification as a Resistance Driver to TKI Therapies in Lung Cancer: Clinical Challenges and Opportunities

MET Amplification as a Resistance Driver to TKI Therapies in Lung Cancer: Clinical Challenges and Opportunities

Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?

Plasma ddPCR for the detection of MET amplification in advanced NSCLC patients: a comparative real-world study

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