|Amino Acid Change||M362T|
|Transcript ID (GRCh37/hg19)||ENST00000318493|
|Tumor Type||Primary Site|
MET is frequently overexpressed in glioblastomas (GBM), and some gliomas show hepatocyte growth factor (HGF) autocrine activation of the MET signaling pathway. Several studies have found that HGF and MET are expressed at higher levels in human gliomas than in control brain tissue, and that expression levels correlate with tumor grade. Some studies have shown that the HGF expression in high-grade (WHO Grade III--IV) tumors was significantly higher than in low-grade (WHO I--II) tumors. Similarly, coexpression of HGF and MET is observed more frequently in Grade IV GBM than in low-grade glioma, consistent with the contribution of an HGF/MET autocrine loop to malignant progression in these tumors. However, MET sequence alterations have been rare. The MET M362T variant is classified as a benign/likely benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/93565/). These results should be interpreted in the clinical context.
The Mesenchymal Epithelial Transition (MET) proto-oncogene encodes the MET receptor tyrosine kinase, also called c-MET or hepatocyte growth factor (HGF) receptor. MET is a ubiquitously expressed cell surface receptor that leads to the activation of several downstream intracellular pathways which promote cellular growth and proliferation, motility, migration and angiogenesis. Dysregulation of MET via gene amplification, germline or somatic mutations or receptor overexpression has been observed in a variety of epithelial cancers, including breast prostate cancer, non-small cell lung cancer, renal papillary carcinoma, hepatocellular and gastric carcinomas. Genetic alterations in MET have been identified in 0.4% of thyroid carcinomas. The prognostic and predictive significance of MET mutations in thyroid cancer is not clear and correlation with other clinical and laboratory findings is necessary. M362T has been identified in the scientific literature, but has not been biochemically characterized and therefore, its effect on protein function is unknown. This variant is reported as a benign/likely benign germline variant in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/93565).