ArticleCancer discovery2015
Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04270591 (A Phase Ib/II, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Glumetinib), which is not on this map. Cited by 437 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase Ib/II, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Glumetinib (SCC244), a Selective MET Inhibitor in Patients With Advanced Non-Small Cell Lung Cancer Harboring MET-alterations
Who cites it
437 citing papers in PubMed, 1 synthesis or guideline pooled it, 791 citations in OpenAlex.
- Efficacy and safety of tepotinib in MET‑altered non‑small cell lung cancer: a meta-analysis.Scientific reports · 2026Pooled it
- Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial.Signal transduction and targeted therapy · 2024Trial
- Phase 2 trial of crizotinib in Japanese patients with advanced NSCLC harboring a MET gene alteration: a Co-MET study.International journal of clinical oncology · 2024Trial
- Phase I Study Evaluating Glesatinib (MGCD265), An Inhibitor of MET and AXL, in Patients with Non-small Cell Lung Cancer and Other Advanced Solid Tumors.Targeted oncology · 2023Trial
- Exposure-response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations.Cancer chemotherapy and pharmacology · 2022Trial
- Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Fast tumor accumulation and payload release of c-Met targeting aptamer-drug conjugate enables robust anti-tumor efficacy.Cell reports. Medicine · 2026Article
- Review
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Artificial intelligence-based diagnostic model for identifying PTPRZ1-MET fusion in a clinically defined secondary glioblastoma cohort.Molecular biomedicine · 2026Article
- A Noncanonical MET Exon 14 Splice-Site Variant in Pulmonary Sarcomatoid Carcinoma With Response to Capmatinib.Thoracic cancer · 2026Article
- Pitfalls in Detecting MET Exon 14 Skipping Variants by DNA- and RNA-Based Next-Generation Sequencing Technologies in a Large Real-World Cohort and Results of the First Multinational External Quality Assessment Schemes.The Journal of molecular diagnostics : JMD · 2026Article
- Targeting non-small cell lung cancer: Molecular mechanisms and clinical studies (Review).Oncology letters · 2026Review
- Targeting MET in 2025: From Exon 14 Skipping to MET-Amplified Acquired Resistance in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Review
- Real-World Evaluation of Next-Generation Sequencing in Lung Cancer: Associations Between Histological Subtypes and Genomic Alterations.Current issues in molecular biology · 2026Article
- MYC contributes to targeted therapy resistance in lung cancers driven by MET exon 14-skipping alteration.NPJ precision oncology · 2026Article
- MET fusions and splicing variants in glioma: a landscape integrating clinical, pathological, and survival features.The journal of pathology. Clinical research · 2026Article
- Successful treatment with tepotinib followed by pembrolizumab in pulmonary pleomorphic carcinoma harbouring aOncology letters · 2026Article
- Crizotinib in Patients with Tumors with MET Amplification or Exon 14 Deletion: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols C1 and C2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- The actionable transcriptome: a framework for incorporating RNA sequencing into precision oncology.Nature reviews. Clinical oncology · 2026Review
377 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
38 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledFocal amplification and activating point mutation of the MET gene are well-characterized oncogenic drivers that confer susceptibility to targeted MET inhibitors. Recurrent somatic splice site alterations at MET exon 14 (METex14) that result in exon skipping and MET activation have been characterized, but their full diversity and prevalence across tumor types are unknown. Here, we report analysis of tumor genomic profiles from 38,028 patients to identify 221 cases with METex14 mutations (0.6%), including 126 distinct sequence variants. METex14 mutations are detected most frequently in lung adenocarcinoma (3%), but also frequently in other lung neoplasms (2.3%), brain glioma (0.4%), and tumors of unknown primary origin (0.4%). Further in vitro studies demonstrate sensitivity to MET inhibitors in cells harboring METex14 alterations. We also report three new patient cases with METex14 alterations in lung or histiocytic sarcoma tumors that showed durable response to two different MET-targeted therapies. The diversity of METex14 mutations indicates that diagnostic testing via comprehensive genomic profiling is necessary for detection in a clinical setting. SIGNIFICANCE: Here we report the identification of diverse exon 14 splice site alterations in MET that result in constitutive activity of this receptor and oncogenic transformation in vitro. Patients whose tumors harbored these alterations derived meaningful clinical benefit from MET inhibitors. Collectively, these data support the role of METex14 alterations as drivers of tumorigenesis, and identify a unique subset of patients likely to derive benefit from MET inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.