Gene | MET |
Variant | missense |
Amino Acid Change | T1010I |
Transcript ID (GRCh37/hg19) | ENST00000318493 |
Codon | 1010 |
Exon | 14 |
Germline/Somatic? | Somatic |
Tumor Type | Primary Site |
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The MET p.T1010I variant has been reported in some tumor types and also has been reported as a germline variant present in less than 1% of the general population. Its role in tumor development and progression continues to be studied. The utility of MET pathway inhibitors also continues to be explored.
The p.T1010I mutation, in the cytoplasmic juxtamembrane domain of MET has been shown to increase growth factor independent proliferation and motility in vitro in tumor cell lines in some studies. This mutation has seen more frequently in thyroid carcinomas than in the goiter controls. But its significance has been challenged by other studies which report a low incidence of T1010I mutation in both tumors and controls and not resulting in an enhanced c-MET phosphorylation. The utility of MET pathway inhibitors also continues to be explored. This variant has also been reported as a germline variant present in less than 1% of the general population. Its role in tumor development and progression continues to be studied. Due to conflicting reports of pathogenicity, this variant best characterized as a variant of uncertain significance (VUS) (https://www.ncbi.nlm.nih.gov/clinvar/variation/41624/).
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 p.T1010I mutation, in the cytoplasmic juxtamembrane domain of MET has been reported in some tumor types and also has been reported as a germline variant present in less than 1% of the general population. Its role in tumor development and progression continues to be studied. The utility of MET pathway inhibitors also continues to be explored.
The p.T1010I mutation, in the cytoplasmic juxtamembrane domain of MET has been shown to increase growth factor independent proliferation and motility in vitro in tumor cell lines in some studies. Approximately 2% of adenocarcinomas of the stomach harbor MET mutations. The utility of MET pathway inhibitors also continues to be explored. This variant has also been reported as a germline variant present in less than 1% of the general population. Its role in tumor development and progression continues to be studied. Due to conflicting reports of pathogenicity, this variant best characterized as a variant of uncertain significance (VUS) https://www.ncbi.nlm.nih.gov/clinvar/variation/41624/.
MET is a receptor tyrosine kinase that has been shown to frequently be altered (mutation or amplification) in various cancers, leading to overexpression. The p.T1010I mutation, in the cytoplasmic juxtamembrane domain of MET has been shown to increase growth factor independent proliferation and motility in vitro in tumor cell lines in some studies. However, the functional effect of T1010I is conflicting, as it has been reported both to have phosphorylation level and transforming capacity similar to wild-type Met protein (PMID: 20670955) This variant has also been reported as a germline variant present in less than 1% of the general population. Its role in tumor development and progression continues to be studied. Due to conflicting reports of pathogenicity, this variant best characterized as a variant of uncertain significance (VUS) (https://www.ncbi.nlm.nih.gov/clinvar/variation/41624/).