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• W2019656564 abstract "MET has gained interest as a therapeutic target for a number of malignancies because of its involvement in tumorigenesis, invasion and metastasis. At present, a number of inhibitors, both antibodies against MET or its ligand hepatocyte growth factor, and small molecule MET tyrosine kinase inhibitors are in clinical trials. We here describe a novel variant of MET that is expressed in 6% of high-grade gliomas. Characterization of this mutation in a glioma cell line revealed that it consists of an intronic deletion, resulting in a splice event connecting an intact splice donor site in exon 6 with the next splice acceptor site being that of exon 9. The encoded protein lacks parts of the extracellular IPT domains 1 and 2, encoded by exons 7 and 8, resulting in a novel pseudo-IPT and is named MET(Δ7-8). MET(Δ7-8) is located predominantly in the cytosol and is constitutively active. The auto-activating nature of MET(Δ7-8), in combination with a lack of transmembrane localization, renders MET(Δ7-8) not targetable using antibodies, although the protein is efficiently deactivated by MET-specific tyrosine kinase inhibitors. Testing of MET-expressing tumors for the presence of this variant may be important for treatment decision making." @default.
• W2019656564 created "2016-06-24" @default.
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• W2019656564 date "2015-04-11" @default.
• W2019656564 modified "2023-10-12" @default.
• W2019656564 title "Identification of a novel MET mutation in high-grade glioma resulting in an auto-active intracellular protein" @default.
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• W2019656564 doi "https://doi.org/10.1007/s00401-015-1420-5" @default.
• W2019656564 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4469304" @default.
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