ArticleCancer discovery2024
Activating Point Mutations in the MET Kinase Domain Represent a Unique Molecular Subset of Lung Cancer and Other Malignancies Targetable with MET Inhibitors.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Capmatinib for High-Level MET-Amplified Metastatic Gastric Cancer Identified by Comprehensive Genomic Profiling: A Case Report and Literature Review.Journal of gastrointestinal cancer · 2026Review
- Clinical applications of antibody-drug conjugates in advanced non-small cell lung cancer.Frontiers in immunology · 2026Review
- First-Line MET Tyrosine Kinase Inhibitors versus Immunotherapy ± Chemotherapy for Patients with MET Exon 14 Skipping Mutant Metastatic NSCLC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Resistance to Allosteric Inhibitors.Journal of molecular biology · 2025Review
- Tyrosine-Mediated Static and Dynamic Quenching of a Receptor Tyrosine Kinase Biosensor Reveals Inhibitor Binding Modes and Kinase Conformations.ACS chemical biology · 2025Article
- Advances in molecular pathology and therapy of non-small cell lung cancer.Signal transduction and targeted therapy · 2025Review
- Responsiveness of different MET tumour alterations to type I and type II MET inhibitors.Clinical and translational medicine · 2025Article
- Prospective Evaluation of Structure-Based Simulations Reveal Their Ability to Predict the Impact of Kinase Mutations on Inhibitor Binding.The journal of physical chemistry. B · 2025Article
- The expanding role of the receptor tyrosine kinase MET as a therapeutic target in non-small cell lung cancer.Cell reports. Medicine · 2025Review
- Prospective evaluation of structure-based simulations reveal their ability to predict the impact of kinase mutations on inhibitor binding.bioRxiv : the preprint server for biology · 2025Article
- Article
- MET Exon 14 Skipping and Novel Actionable Variants: Diagnostic and Therapeutic Implications in Latin American Non-Small-Cell Lung Cancer Patients.International journal of molecular sciences · 2024Article
- Mapping kinase domain resistance mechanisms for the MET receptor tyrosine kinase via deep mutational scanning.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
41 authors.
Funding
Abstract
Activating point mutations in the MET tyrosine kinase domain (TKD) are oncogenic in a subset of papillary renal cell carcinomas. Here, using comprehensive genomic profiling among >600,000 patients, we identify activating MET TKD point mutations as putative oncogenic driver across diverse cancers, with a frequency of ∼0.5%. The most common mutations in the MET TKD defined as oncogenic or likely oncogenic according to OncoKB resulted in amino acid substitutions at positions H1094, L1195, F1200, D1228, Y1230, M1250, and others. Preclinical modeling of these alterations confirmed their oncogenic potential and also demonstrated differential patterns of sensitivity to type I and type II MET inhibitors. Two patients with metastatic lung adenocarcinoma harboring MET TKD mutations (H1094Y, F1200I) and no other known oncogenic drivers achieved confirmed partial responses to a type I MET inhibitor. Activating MET TKD mutations occur in multiple malignancies and may confer clinical sensitivity to currently available MET inhibitors. Significance: The identification of targetable genomic subsets of cancer has revolutionized precision oncology and offers patients treatments with more selective and effective agents. Here, we demonstrate that activating, oncogenic MET tyrosine kinase domain mutations are found across a diversity of cancer types and are responsive to MET tyrosine kinase inhibitors.
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