ArticleCurrent pharmaceutical design2013
Detection and therapeutic implications of c-Met mutations in small cell lung cancer and neuroendocrine tumors.
Article in Current pharmaceutical design, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Identification of Actionable Gene Variants in Pulmonary Large-Cell Neuroendocrine Carcinoma: A Real-World Analysis of a Polish Cohort.International journal of molecular sciences · 2026Article
- Targeting mesenchymal-epithelial transition factor signaling in cancer: from genetic alterations to clinical advances and future prospects.Molecular biology reports · 2025Review
- MET and SLFN11 as a Players in the SCLC Molecular Subtyping Game.International journal of molecular sciences · 2025Article
- Article
- The Emerging Role of c-Met in Carcinogenesis and Clinical Implications as a Possible Therapeutic Target.Journal of oncology · 2022Review
- Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single-center retrospective cohort study and literature review.Oncology letters · 2020Article
- Recent progress in mapping the emerging landscape of the small-cell lung cancer genome.Experimental & molecular medicine · 2019Review
- Review
- Impact of MET inhibition on small-cell lung cancer cells showing aberrant activation of the hepatocyte growth factor/MET pathway.Cancer science · 2017Article
- Pharmacodynamic Response of the MET/HGF Receptor to Small-Molecule Tyrosine Kinase Inhibitors Examined with Validated, Fit-for-Clinic Immunoassays.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Targeted drugs in small-cell lung cancer.Translational lung cancer research · 2016Review
- Article
- Biology of MET: a double life between normal tissue repair and tumor progression.Annals of translational medicine · 2015Review
- Retrospective Review of MET Gene Mutations.Oncoscience · 2015Article
- Therapeutic biomarkers in lung neuroendocrine neoplasia.Endocrine pathology · 2014Review
- Single-nucleotide polymorphism rs41736 located in MET was significantly associated with prognosis of small cell lung cancer patients.Medical oncology (Northwood, London, England) · 2014Article
- Oncogenic codon 13 NRAS mutation in a primary mesenchymal brain neoplasm and nevus of a child with neurocutaneous melanosis.Acta neuropathologica communications · 2014Article
- MET and Small-Cell Lung Cancer.Cancers · 2014Review
- MET nucleotide variations and amplification in advanced ovarian cancer: characteristics and outcomes with c-Met inhibitors.Oncoscience · 2014Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundWe evaluated the mutation status of c-Met in small cell lung cancer (SCLC) and neuroendocrine tumors (NET), for which relatively limited therapeutic targets have been explored. MATERIALS AND
methodsc-Met was re-sequenced using cell lines and clinical samples. For in vitro studies, DNA constructs containing a juxtamembrane domain (JMD) and tyrosine kinase domain (TKD) were generated. Detected mutations were introduced into the construct and effects on c-Met phosphorylation and interaction with tyrosine kinase inhibitor drugs BMS777607 and SU11274 were assessed.
results97 specimens were analyzed: 13 SCLC and 2 pulmonary carcinoid cell lines, 46 SCLC and 36 NET clinical specimens. Mutations were only detected in the JMD. No mutations were detected in the TKD. Found mutations consisted of the previously reported R988C and T1010I mutations. One novel JMD mutation, P996S, was detected in a SCLC specimen. The mutation rate in SCLC cell lines was 25% (31% including a derivative cell line), and 6.5% in clinical specimens. The mutation rate in NET was 8.3%. In vitro, there were no differences between wild type, R988C or T1010I mutants regarding c-Met phosphorylation at Y1003, located in the JMD, and at Y1234/1235, located in the TKD. BMS777607 and SU11274 were shown to inhibit phosphorylation of c-Met in wild type and R988C and T1010I mutants in a similar fashion.
conclusionsIn SCLC and neuroendocrine tumors MET mutations are relatively rare. Detected mutations were located in the juxtamembrane domain and were of no functional relevance as they did not influence c-Met phosphorylation, regardless of TKI treatment.
Indexed as
Identifiers
22973954PMC7569720W2158494564What OpenQuestion holds
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.