The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing
Introduction: MET exon 14 (METex14) skipping mutations are observed in approximately 0.9% to 4% of patients with NSCLC. This study aimed to compare the detection rates of METex14 skipping in Chinese patients with lung cancer using DNA-based next-generation sequencing (NGS) with capture-based library...
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Elsevier
2025-07-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364325000426 |
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| author | Jia Liao, MD Song Wu, MD Yi Min, MD Yiran Li, MD Yuanhang Nie, MD Quwen Chen, MD Zhiliang Mao, MD Qinglan Zong, MS Ning Gao, MS Ding Zhang, PhD Weiquan Liang, MD |
| author_facet | Jia Liao, MD Song Wu, MD Yi Min, MD Yiran Li, MD Yuanhang Nie, MD Quwen Chen, MD Zhiliang Mao, MD Qinglan Zong, MS Ning Gao, MS Ding Zhang, PhD Weiquan Liang, MD |
| author_sort | Jia Liao, MD |
| collection | DOAJ |
| description | Introduction: MET exon 14 (METex14) skipping mutations are observed in approximately 0.9% to 4% of patients with NSCLC. This study aimed to compare the detection rates of METex14 skipping in Chinese patients with lung cancer using DNA-based next-generation sequencing (NGS) with capture-based library construction and synchronous DNA-based and RNA-based NGS with amplicon-based library construction. Methods: A total of 11,330 tissue samples from 11,330 Chinese patients with lung cancer were included in the study to confirm the presence of METex14 skipping. Simultaneously, MET immunohistochemistry testing was performed on 30 patients. Results: The highest detection rate of METex14 skipping was observed in the synchronous DNA and RNA-based NGS with amplicon-based library construction, reaching 2.20%. A total of 45 different variants leading to METex14 skipping were detected at the DNA level. These variants were widely distributed across a 197–base pair DNA sequence. In the overall population, the incidence of METex14 skipping was significantly higher in individuals aged 60 years and above (p < 0.0001) and needle biopsy samples (p < 0.0001) and reported no significant association with gender and tumor location. A positive correlation was observed between microsatellite instability–high and METex14 skipping (p < 0.0001). Conclusions: The mutations causing METex14 skipping exhibit diversity in terms of variant types and are widely distributed across various genomic regions. Synchronous DNA-based and RNA-based NGS is considered the optimal method for detecting METex14 skipping. Furthermore, METex14 skipping is enriched in specific populations, including individuals aged 60 years and above, with advanced-stage disease and a microsatellite instability-high status. |
| format | Article |
| id | doaj-art-58ec45fc1cd04d33a3094d07b08c93a2 |
| institution | DOAJ |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj-art-58ec45fc1cd04d33a3094d07b08c93a22025-08-20T03:15:20ZengElsevierJTO Clinical and Research Reports2666-36432025-07-016710082610.1016/j.jtocrr.2025.100826The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation SequencingJia Liao, MD0Song Wu, MD1Yi Min, MD2Yiran Li, MD3Yuanhang Nie, MD4Quwen Chen, MD5Zhiliang Mao, MD6Qinglan Zong, MS7Ning Gao, MS8Ding Zhang, PhD9Weiquan Liang, MD10The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Guangdong, People's Republic of ChinaDepartment of Thoracic Surgery, The Affiliated Jiangyin Hospital of Nantong University, Jiangsu, People's Republic of ChinaThe First Clinical Medical College, Guangdong Medical University, Guangdong, People's Republic of ChinaDepartment of Respiratory and Critical Care Medicine, Foshan Second People's Hospital, Guangdong, People's Republic of ChinaDepartment of Respiratory and Critical Care Medicine, Foshan Second People's Hospital, Guangdong, People's Republic of ChinaThe First Clinical Medical College, Guangdong Medical University, Guangdong, People's Republic of ChinaDepartment of Respiratory and Critical Care Medicine, Foshan Second People's Hospital, Guangdong, People's Republic of ChinaDepartment of Medical Affairs, 3D Medicines Inc., Shanghai, People's Republic of ChinaDepartment of Medical Affairs, 3D Medicines Inc., Shanghai, People's Republic of ChinaDepartment of Medical Affairs, 3D Medicines Inc., Shanghai, People's Republic of ChinaDepartment of Respiratory and Critical Care Medicine, Foshan Second People's Hospital, Guangdong, People's Republic of China; Corresponding author. Address for correspondence: Weiquan Liang, MD, Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Foshan (Affiliated Foshan Hospital of Southern Medical University), Weiguo Lu 78, Foshan City, Guangdong Province 528000, People's Republic of China.Introduction: MET exon 14 (METex14) skipping mutations are observed in approximately 0.9% to 4% of patients with NSCLC. This study aimed to compare the detection rates of METex14 skipping in Chinese patients with lung cancer using DNA-based next-generation sequencing (NGS) with capture-based library construction and synchronous DNA-based and RNA-based NGS with amplicon-based library construction. Methods: A total of 11,330 tissue samples from 11,330 Chinese patients with lung cancer were included in the study to confirm the presence of METex14 skipping. Simultaneously, MET immunohistochemistry testing was performed on 30 patients. Results: The highest detection rate of METex14 skipping was observed in the synchronous DNA and RNA-based NGS with amplicon-based library construction, reaching 2.20%. A total of 45 different variants leading to METex14 skipping were detected at the DNA level. These variants were widely distributed across a 197–base pair DNA sequence. In the overall population, the incidence of METex14 skipping was significantly higher in individuals aged 60 years and above (p < 0.0001) and needle biopsy samples (p < 0.0001) and reported no significant association with gender and tumor location. A positive correlation was observed between microsatellite instability–high and METex14 skipping (p < 0.0001). Conclusions: The mutations causing METex14 skipping exhibit diversity in terms of variant types and are widely distributed across various genomic regions. Synchronous DNA-based and RNA-based NGS is considered the optimal method for detecting METex14 skipping. Furthermore, METex14 skipping is enriched in specific populations, including individuals aged 60 years and above, with advanced-stage disease and a microsatellite instability-high status.http://www.sciencedirect.com/science/article/pii/S2666364325000426Lung cancerSecond generation sequencingMETex14 skippingAmplicon-based library constructionCapture-based library construction |
| spellingShingle | Jia Liao, MD Song Wu, MD Yi Min, MD Yiran Li, MD Yuanhang Nie, MD Quwen Chen, MD Zhiliang Mao, MD Qinglan Zong, MS Ning Gao, MS Ding Zhang, PhD Weiquan Liang, MD The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing JTO Clinical and Research Reports Lung cancer Second generation sequencing METex14 skipping Amplicon-based library construction Capture-based library construction |
| title | The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing |
| title_full | The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing |
| title_fullStr | The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing |
| title_full_unstemmed | The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing |
| title_short | The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing |
| title_sort | landscape of met exon 14 skipping mutations in patients with lung cancer identified by next generation sequencing |
| topic | Lung cancer Second generation sequencing METex14 skipping Amplicon-based library construction Capture-based library construction |
| url | http://www.sciencedirect.com/science/article/pii/S2666364325000426 |
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